Int J Immunopharmacol, 1999 Mar, 21(3), 161 - 76 Atiprimod (SK&F 106615), a novel macrophage targeting agent, enhances alveolar macrophage candidacidal activity and is not immunosuppressive in Candida-infected mice; Badger AM et al.; Azaspiranes are novel macrophage-targeting agents with activity in preclinical animal models of autoimmune disease and transplantation . The purpose of this work was to determine the effects of atiprimod (SK&F 106615), an azaspirane being developed for the treatment of rheumatoid arthritis, on rat pulmonary alveolar macrophage (AM) function and immunocompetance in Candida-infected mice . AM from rats treated with 20 mg/kg/day of atiprimod for 15 days demonstrated enhanced killing of Candida albicans ex vivo . Concentration-dependent increases in candidacidal activity were also observed as early as one hour after exposure in vitro in AM from untreated normal rats . Treatment of AM with atiprimod in vitro did not increase particulate-stimulated superoxide production or phagocytosis of Candida but decreased their ability to concentrate acridine orange, indicating an increase in lysosomal pH . Increased candidacidal activity was inhibited by superoxide dismutase and catalase, suggesting a role for reactive oxygen intermediates (ROI) . Atiprimod also increased free radical-mediated killing of Candida in the presence of H2O2, iron and iodide in a cell-free system . These findings indicated that treatment with atiprimod increased the candidacidal activity of rat AM in a free radical-dependent manner . The data also suggested that atiprimod did not increase ROI production by AM, but rather increased the efficiency of radical-mediated killing . This increase may be caused by cyclization of atiprimod, facilitating electron transfer and peroxidation of lipid membranes . In vivo studies in Candida-infected CBA mice showed that atiprimod (10 mg/kg/day), did not compromise immune function in the infected mice and could be differentiated from prototypical immunosuppressive compounds used for treatment of autoimmune diseases. J Antibiot (Tokyo), 1999 Mar, 52(3), 311 - 8 Aspirochlorine: a highly selective and potent inhibitor of fungal protein synthesis; Monti F et al.; Aspirochlorine, a compound belonging to the gliotoxin family of compounds, exhibits antifungal and antibacterial activity but its mechanism of action remains unknown . In this study we show that aspirochlorine inhibits the pathogenic fungus Candida albicans by acting on fungal protein synthesis . The compound selectively inhibits cell-free protein synthesis when using a C . albicans system, but does not inhibit this synthesis in vitro when tested with bacterial and mammalian systems . Moreover, in intact C . albicans cells, aspirochlorine inhibits protein synthesis but does not inhibit chitin, DNA or glucan synthesis though at high concentrations some inhibition of RNA synthesis is observed . By contrast, in intact Bacillus subtilis cells, aspirochlorine did not inhibit protein, DNA, or cell wall synthesis though it significantly inhibited RNA synthesis . Furthermore, using heterologous systems (mammalian ribosomes and C . albicans cytosolic factors) the data suggest that the inhibitory action of aspirochlorine is not exerted through a direct interaction with C . albicans EF-1 or EF-2. J Nat Prod, 1999 May, 62(5), 767 - 9 Two auronols from Pseudolarix amabilis; Li XC et al.; Two new auronols, amaronols A (1) and B (2), were isolated from the bark of Pseudolarix amabilis, along with pseudolaric acid B (3), pseudolaric acid C (4), demethoxydeacetoxy-pseudolaric acid B (5), pseudolaric acid B-beta-D-glucoside (6), pseudolaric acid A-beta-D-glucoside (7), and myricetin (8) . The structures of amaronols A and B were established by spectral data interpretation as 2,4,6-trihydroxy-2-{(3',4',5'-trihydroxyphenyl) methyl}-3(2H)-benzofuranone and 2,4,6-trihydroxy-2-{(3', 5'-dihydroxy-4'-methoxyphenyl) methyl}-3(2H)-benzofuranone, respectively . Antimicrobial testing results of the eight compounds indicated that only pseudolaric acid B was active against Candida albicans (MIC, 3.125 microg/mL; MFC, 6.25 microg/mL), while myricetin was marginally active against Trichophyton mentagrophytes (MIC, 50 microg/mL). J Nat Prod, 1999 May, 62(5), 678 - 80 Antifungal metabolites from the marine sponge Pachastrissa sp.: new bengamide and bengazole derivatives; Fernandez R et al.; This paper reports the studies of components of an undescribed sponge in the genus Pachastrissa sp., collected along the Djibouti coast . The extract showed activity against Candida albicans . Six new bengazoles (1-6) and a new bengamide, named bengamide L (16), in addition to the known bengazoles (7-11), bengamides A (12), B (13), E (14), and F (15), and a lactone (17) are described in this paper . All structures were determined on the basis of spectroscopic studies. Electrophoresis, 1999 Apr-May, 20(4-5), 1001 - 10 Two-dimensional gel electrophoresis as analytical tool for identifying Candida albicans immunogenic proteins; Pitarch A et al.; This paper reports the usefulness of two-dimensional gel electrophoresis followed by Western blotting with sera from patients with systemic candidiasis in the identification of the major Candida albicans antigens . In order to have different patterns of protein expression and subcellular localization, three types of protein preparations were obtained: cytoplasmic extracts, protoplast lysates and proteins secreted by protoplasts regenerating their cell wall . These proteins were separated by high-resolution two-dimensional electrophoresis using an immobilized pH gradient . Western blotting with sera from patients with systemic candidiasis allowed the detection of more than 18 immunoreactive proteins . Some of these proteins had different isoforms . All sera reacted with at least three C . albicans proteins and the most reactive serum detected up to eleven proteins . Some of these antigens, e.g., enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), have been identified on the 2-D map . The most reactive proteins were enolase and a 34 kDa protein in the acidic part of the gel (pI 4-4.4) that was only detected in regenerating protoplast-secreted proteins . The identification of all these antigens would be useful for the development of diagnostic strategies. J Drug Target, 1999, 6(5), 361 - 72 Light and electron microscopic findings in a model of human cutaneous candidosis based on reconstructed human epidermis following the topical application of different econazole formulations; Schaller M et al.; The effects of two commercially available econazole formulations (econazole nitrate cream, econazole liposome gel) on uninfected reconstructed human epidermis and on a model of human cutaneous candidosis were investigated . The morphological alterations of the reconstructed epidermis after infection and treatment were analysed with light and electron microscopy . The most important Candida albicans-specific alterations of the recently established in vitro model of human cutaneous candidosis were scaling, hyperkeratosis, parakeratosis, dyskeratosis and spongiosis . A single application of the cream to the uninfected reconstructed epidermis caused more epidermal barrier damage and irritative toxic effects than the liposome gel . Treatment of the modelled human cutaneous candidosis with the cream also resulted in increased toxic effects, e.g., enhancement of scaling with invasion of Candida albicans blastospores into the stratum corneum and intracellular vacuoles . After application of the liposomal preparation invasion of Candida albicans in the stratum corneum could not be detected and toxic effects were reduced . Some of the Candida albicans-specific alterations such as hyperkeratosis, focal thickening of the stratum corneum, dyskeratosis and parakeratosis were completely eliminated . The liposomal formulation increased slightly the morphological alterations of the blastospores . Remnants of the cream formulation could be detected only very rarely in the stratum corneum or the blastospores . The liposomal preparation showed a strong affinity for the Candida albicans cells and the stratum corneum . Intact liposomes could even be observed in the intercellular spaces of the upper stratum corneum . As successful treatment depends on the ability to target the liposomal agent to the wanted site of action, this might be useful for more effective treatment of cutaneous candidosis. Diagn Microbiol Infect Dis, 1999 May, 34(1), 19 - 25 Distribution of Candida albicans genotypes among family members; Mehta SK et al.; Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast . An enrichment procedure provided a twofold increase in the recovery of C . albicans from mouthwash specimens . Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members . Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis . DNA fingerprinting of C . albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype . No two families shared the same strain, and two or more members of a family commonly shared the same strain . Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families . Genotypes of isolates from husband and wife differed from one another in five families . All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power. Crit Rev Microbiol, 1999, 25(1), 1 - 17 Molecular mechanisms of chromosomal rearrangement in fungi; Fierro F et al.; Both sexual and asexual fungi undergo chromosomal rearrangements, which are the main cause of karyotype variability among the populations . Different recombination processes can produce chromosomal reorganizations, both during mitosis and meiosis, but other mechanisms operate to limit the extent of the rearrangements; some of these mechanisms, such as the RIP (repeat-induced point mutations) of Neurospora crassa, have been well established for sexual fungi . In laboratory strains, treatments such as mutation and transformation enhance the appearance of chromosomal rearrangements . Different DNA sequences present in fungal genomes are able to promote these reorganizations; some of these sequences are involved in well-regulated processes (e.g., site-specific recombination) but most of them act simply as substrates for recombination events leading to DNA rearrangements . In Penicillium chrysogenum we have found that short specific DNA sequences are involved in tandem reiterations leading to amplification of the cluster of the penicillin biosynthesis genes . In some cases, specific chromosomal rearrangements have been associated with particular phenotypes (as occurs in adaptive-like mutants of Candida albicans and Candida stellatoidea), and they may play a role in genetic variability for environmental adaptation. Clin Exp Immunol, 1999 May, 116(2), 291 - 8 Effects of glycyrrhizin, an active component of licorice roots, on Candida albicans infection in thermally injured mice; Utsunomiya T et al.; Due to the generation of burn-associated CD8+ CD11b+ TCR gamma/delta+ type 2 T cells (burn-associated type 2 T cells), the susceptibility of thermally injured mice to infection with C . albicans has been shown to be increased by up to 50-fold when compared with normal mice . Glycyrrhizin (GR), an active component of licorice roots, reduced the susceptibility of thermally injured mice to C . albicans infection to levels observed in normal mice . Thermally injured mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C . albicans infection . The following demonstrated that susceptibility to fungal infection was similar in thermally injured mice and normal mice inoculated with T6S cells (a clone of burn-associated type 2 T cells) . This susceptibility of T6S mice (normal mice inoculated with T6S cells) was reversible by (i) administration of GR, (ii) inoculation of CD4+ T cells from GR-treated mice, and (iii) injection of a mixture of MoAbs targeted against type 2 cytokines (IL-4 and IL-10) . After stimulation with anti-CD3 MoAb, splenic T cells from thermally injured and T6S mice, treated with GR or inoculated with CD4+ T cells from GR-treated mice, did not have type 2 cytokines in culture supernatants . They were present in splenic T cell cultures from thermally injured and T6S mice that were treated with saline or inoculated with naive T cells . These results suggest that GR, by inducing CD4+ T cells which suppress type 2 cytokines produced by burn-associated type 2 T cells, improves the resistance of thermally injured mice to C . albicans . An anti-type 2 T cell action of the CD4+ T cells derived from GR-treated mice was previously described. Microbiol Immunol, 1999, 43(3), 235 - 40 Effective inhibition of Candida albicans growth by the combination of murine peritoneal neutrophils and activated macrophages; Tansho S et al.; The effect of leukocytes on the anti-Candida activity of neutrophils was examined . Murine neutrophils which were purified from casein-induced peritoneal cells inhibited the mycelial growth of Candida albicans . This anti-Candida activity of neutrophils was augmented by the addition of spleen cells prepared from mice pretreated with bacterial lipopolysaccharide 3 hr before, but not from non-treated mice . The population in the spleen cells, which enhanced the anti-Candida activity of neutrophils, was plastic-plate adherent, nylon-fiber columns adherent and anti-Mac-1 antigen-positive . These immunological profiles suggested that the enhancing cells are classified to splenic macrophages . Peritoneal-exudated macrophages from mice treated with lipopolysaccharide also augmented the anti-Candida activity of neutrophils . These results suggest that the anti-Candida activity of neutrophils may be upregulated by activated macrophages. FEBS Lett, 1999 Apr 23, 449(2-3), 105 - 10 A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides; Helmerhorst EJ et al.; The hemolytic and fungicidal activity of a number of cationic antimicrobial peptides was investigated . Histatins and magainins were inactive against human erythrocytes and Candida albicans cells in phosphate buffered saline, but displayed strong activity against both cell types when tested in 1 mM potassium phosphate buffer supplemented with 287 mM glucose . The HC50/IC50 ratio, indicative of the therapeutic index, was about 30 for all peptides tested . PGLa was most hemolytic (HC50 = 0.6 microM) and had the lowest therapeutic index (HC50/IC50 = 0.5) . Susceptibility to hemolysis was shown to increase with storage duration of the erythrocytes and also significant differences were found between blood collected from different individuals . In this report, a sensitive assay is proposed for the testing of the hemolytic activities of cationic peptides . This assay detects subtle differences between peptides and allows the comparison between the hemolytic and fungicidal potency of cationic peptides. Glycobiology, 1999 Jun, 9(6), 533 - 7 Purification and biochemical characterization of two soluble alpha-mannosidases from Candida albicans; Vazquez-Reyna AB et al.; Two soluble alpha-mannosidases, E-I and E-II, were purified from C . albicans yeast cells by a three-step procedure consisting of size exclusion and ion exchange chromatographies in Sepharose CL6B and Mono Q columns, respectively, and preparative nondenaturing electrophoresis . E-I and E-II migrated as monomeric polypeptides of 54.3 and 93.3 kDa in SDS-PAGE, respectively . Some biochemical properties of purified enzymes were investigated by using 4-methylumbelliferyl-alpha-D-mannopyranoside and p-nitrophenyl-alpha-D-mannopyranoside as substrates . Hydrolysis of both substrates by either enzyme was optimum at pH 6.0 with 50 mM Mes-Tris buffer and at 42 degrees C . Apparent Kmvalues for hydrolysis of 4-methylumbelliferyl-alpha-D-mannopyranoside and p-nitrophenyl-alpha-D-mannopyranoside by E-I were 0.83 microM and 2 . 4 mM, respectively . Corresponding values for E-II were 0.25 microM and 1.86 mM . Swansonine and deoxymannojirimicin strongly inhibited the hydrolysis of 4-methylumbelliferyl-alpha-D-mannopyranoside by both enzymes . On the contrary, hydrolysis of p-nitrophenyl-alpha-D-mannopyranoside by E-I and E-II was slightly stimulated or not affected, respectively, by both inhibitors . E-I and E-II did not depend on metal ions although activity of the latter was slightly stimulated by Mn2+and Ca2+in the range of 0.5-2 mM . At the same concentrations, Mg2+was slightly inhibitory of both enzymes . Substrate specificity experiments revealed that both E-I and E-II preferentially cleaved alpha-1,6 and alpha-1,3 linkages, respectively. J Basic Microbiol, 1999, 39(2), 97 - 101 Properties of adenosine deaminase from Candida albicans; Challa A et al.; Adenosine deaminase (ADA; adenosine aminohydrolase, E.C . 3.5.4.4), a purine catabolic enzyme, was studied in Candida albicans, an opportunistic yeast that causes diseases ranging from superficial infections to the deep systemic disease, candidiasis, in immunosuppressed humans . The fungus was grown as a yeast form in LEE's synthetic medium, pH 4.5, at room temperature for various growth periods . Adenosine deaminase (ADA) activity was determined from the cell free extract by measuring the change in absorbance 265 nm resulting from the deamination of adenosine . In yeast form, maximum growth and ADA activity were found at 72 and 24 hours, respectively, whereas in the mycelial form both the growth and ADA activity were maximum after 48 hours . Among the three media tested, tryptic soy broth supported maximum growth and enzyme production, compared to LEE synthetic medium or SABOURAUD dextrose broth . The enzyme was active over the pH range 4-8 and the optimum temperature for ADA activity was found to be 37 degrees C. Clin Exp Allergy, 1999 Jun, 29(6), 824 - 31 Candida albicans mannan- and protein-induced humoral, cellular and cytokine responses in atopic dermatitis patients; Savolainen J et al.; BACKGROUND: The cytokine observed most often in atopic dermatitis (AD) is IL-4, but a role for IL-5 and IFN-gamma in the late and delayed phase reactions has been suggested . In AD with head, neck and shoulder distribution, hypersensitivity to saprophytic yeasts is an important pathogenetic factor . The yeast allergens include both the mannan polysaccharides and the proteins . Mannans are major cross-reacting allergens likely to be involved in the pathogenesis of AD . OBJECTIVE: To characterize the humoral, lymphoproliferative and cytokine (IL-2, 4, 5 and IFN-gamma) responses of peripheral blood mononuclear cells (PBMCs) induced by Candida albicans mannan and protein antigens in AD . METHODS: Fifteen AD patients and seven healthy controls were included . Ficoll-isolated PBMCs were stimulated by PHA and laboratory-generated mannan and protein extracts of C . albicans . Lymphocyte proliferation was measured and cytokine production was studied by ELISA . The antigen-specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST . RESULTS: In AD mannan (P < 0.005) and protein (P < 0.002), specific IgE levels were higher than in healthy controls . Both mannan and protein-specific lymphoproliferations (both: P < 0.02) were higher in AD than in healthy controls . Mannan, but not protein, induced long lasting IL-2 and IL-4 productions from 24 h lasting up to 66-96 h and IL-5 and IFN-gamma productions with elevated levels at 66 and 96 h . The mannan-induced IL-2 (P = 0.015) and IFN-gamma (P < 0.005) were increased in AD as compared with healthy controls . Significant correlations were seen between the protein-induced proliferation responses and both serum total IgE (r = 0.59, P < 0.01) and protein-specific IgE (r = 0.65, P < 0.005) . The mannan-induced IL-2 responses correlated with the specific IgE (r = 0.62, P < 0.01) and proliferation (r = 0.51, P < 0.02) and S-IgE level (r = 0.71, P < 0 . 002) . Mannan-induced IL-4 and IFN-gamma productions also correlated (r = 0.43, P < 0.05) . CONCLUSIONS: C . albicans mannan induced elevated IL-2 and IFN-gamma responses in AD patients . The correlations of the cytokine responses with mannan-induced IgE and proliferation responses suggest that C . albicans mannan induced TH1 type cytokine responses are involved in AD. Rev Esp Quimioter, 1998 Dec, 11(4), 339 - 43 {In vitro activity of fluconazole against Candida albicans isolated from blood culture}; Peman J et al.; The in vitro activity of fluconazole against 65 Candida albicans isolated from blood culture in 1995, 1996 and 1997 was studied by macrodilution and disk diffusion methods . The MIC ranged from 0.03 to 64 microg/ml, with 93.6% of strains being inhibited with 1 microg/ml fluconazole; the mode MIC was 0.25 microg/ml . Using this method, only one strain was resistant and another was susceptible depending on the dose . By diffusion, eight strains were susceptible, 53 intermediate, and four resistant . The strains susceptible by dilution were also susceptible by diffusion, but the strains resistant by diffusion were not always resistant by dilution . We find it therefore useful to determine the MIC of fluconazole to the C . albicans resistant by diffusion. Biotechnol Appl Biochem, 1999 Jun, 29 ( Pt 3), 223 - 7 Generation of a highly immunogenic recombinant enolase of the human opportunistic pathogen Candida albicans; Sandini S et al.; Enolase, a 46 kDa glycolytic enzyme, is an immunodominant antigen of Candida albicans, an important human opportunistic pathogen . The full-length coding sequence of C . albicans enolase gene was subcloned into the prokaryotic expression vector pDS56/RBSII,His6/E- under the control of an inducible promoter to produce a His6-tagged enolase . The recombinant protein was purified to homogeneity by one-step nickel-chelate affinity chromatography . It was recognized by a monoclonal antibody specific for C . albicans enolase, as well as by anti-enolase antibodies present in human sera (IgG) . The recombinant protein promptly elicited antibody in mice and detected immune responses in normal human subjects that were comparable to those generated by the native C . albicans enolase . Thus this new recombinant enolase constitutes a valuable reagent for studying the possible role of this protein in anti-Candida immune response. J Clin Lab Immunol, 1996, 48(1), 1 - 15 Immunological cross reactivity between Candida albicans and human tissue; Vojdani A et al.; An old concept to account for autoimmunity is the existence of immunologic cross reactions, or shared determinants between an exogenous agent and self antigen . To study molecular mimicry between the Candida antigen and an autoantigen, sera from clinical specimens were screened, based on seronegativity or positivity for thyroid, ovary and adrenal antibodies . Compared with tissue antibody negative sera and sera from healthy controls, samples from positive tissue antibody subjects exhibited significantly higher levels of Candida IgG (P < 0.001) IgM (P < 0.001) and IgA (P < 0.01) antibodies . While Candida antibodies were elevated in 60% of tissue antibody positive samples, these antibodies were present in only 7.5% of tissue antibody negative subjects and in 10% of healthy controls . Since PAGE electrophoresis showed similar bands mobility in Candida and different tissues, these positive antibodies and rabbit anti Candida antibodies were reacted in immunodiffusion and Western Blot Assay against Candida and tissue antigens, simultaneously . The results of immunodiffusion showed a clear precipitation line against tissue antigens when rabbit anti Candida or human positive Candida serum was used . Similarly, Western Blot Assays with rabbit or human anti Candida serum showed several positive bands with Candida and one or two positive bands with different tissues . The common antigens were located in the regions of 72 and 36 KD . The 72 KD was detected in capsule antigens, placenta, ovary, adrenal, thymus, liver, pancreas, spleen, brain and kidney, but not in sperm or epithelial cell antigen . The 36 KD antigen was positive in placenta, spleen adrenal, pancreas and capsule tissues . Absorbtion of sera containing high levels of Candida antibodies with tissue antigens caused 10-15% reduction in antibody titers . Moreover, treatment of thyroid antibody positive sera with C . Albicans caused a similar reduction in thyroid antibody levels . These reductions in antibody levels are an additional support for cross reactivity between C . Albicans and mammalian tissues . A demonstration of immunological cross reactivity between Candida and human tissues may be associated with the possible pathogenic role of Candida Albicans in the development of autoimmune diseases which warrants further investigation. J Chemother, 1999 Apr, 11(2), 131 - 6 Nosocomial Candida krusei fungemia in cancer patients: report of 10 cases and review; Krcmery V Jr et al.; The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed . Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy . Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole . However, attributable and crude mortality due to C . krusei fungemias was higher than for C . albicans fungemia . The authors review 172 C . krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C . krusei fungemia from our cancer institute. Mol Cell Biol, 1999 Jun, 19(6), 4019 - 27 A G1 cyclin is necessary for maintenance of filamentous growth in Candida albicans; Loeb JD et al.; Candida albicans undergoes a dramatic morphological transition in response to various growth conditions . This ability to switch from a yeast form to a hyphal form is required for its pathogenicity . The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch . Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida . G1 cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S . cerevisiae . We show that C . albicans CLN1 (CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S . cerevisiae . To investigate whether G1 cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C . albicans, we mutated CaCLN1 . Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression . The Cacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media . Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium . Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues. J Bacteriol, 1999 May, 181(10), 3058 - 68 Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans; Alonso-Monge R et al.; The relevance of the mitogen-activated protein (MAP) kinase Hog1p in Candida albicans was addressed through the characterization of C . albicans strains without a functional HOG1 gene . Analysis of the phenotype of hog1 mutants under osmostressing conditions revealed that this mutant displays a set of morphological alterations as the result of a failure to complete the final stages of cytokinesis, with parallel defects in the budding pattern . Even under permissive conditions, hog1 mutants displayed a different susceptibility to some compounds such as nikkomycin Z or Congo red, which interfere with cell wall functionality . In addition, the hog1 mutant displayed a colony morphology different from that of the wild-type strain on some media which promote morphological transitions in C . albicans . We show that C . albicans hog1 mutants are derepressed in the serum-induced hyphal formation and, consistently with this behavior, that HOG1 overexpression in Saccharomyces cerevisiae represses the pseudodimorphic transition . Most interestingly, deletion of HOG1 resulted in a drastic increase in the mean survival time of systemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi . This finding has potential implications in antifungal therapy. Mol Microbiol, 1999 May, 32(3), 547 - 56 Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination; Morschhauser J et al.; The genetic manipulation of the human fungal pathogen Candida albicans is difficult because of its diploid genome, the lack of a known sexual phase and its unusual codon usage . We devised a new method for sequential gene disruption in C . albicans that is based on the repeated use of the URA3 marker for selection of transformants and its subsequent deletion by FLP-mediated, site-specific recombination . A cassette was constructed that, in addition to the URA3 selection marker, contained an inducible SAP2P-FLP fusion and was flanked by direct repeats of the minimal FLP recognition site (FRT) . This URA3 flipper cassette was used to generate homozygous C . albicans mutants disrupted for both alleles of either the CDR4 gene, encoding an ABC transporter, or the MDR1 gene, encoding a membrane transport protein of the major facilitator superfamily . After insertion of the URA3 flipper into the first copy of the target gene, the whole cassette could be efficiently excised by induced FLP-mediated recombination, leaving one FRT site in the disrupted allele of the target gene . The URA3 flipper was then used for another round of mutagenesis to disrupt the second allele . Deletion of the cassette from primary and secondary transformants occurred exclusively by intrachromosomal recombination of the FRT sites flanking the URA3 flipper, whereas interchromosomal recombination between FRT sites on the homologous chromosomes was never observed . This new gene disruption strategy facilitates the generation of specific, homozygous C . albicans mutants as it eliminates the need for a negative selection scheme for marker deletion and minimizes the risk of mitotic recombination in sequential disruption experiments. Mol Microbiol, 1999 May, 32(3), 533 - 46 Host-induced, stage-specific virulence gene activation in Candida albicans during infection; Staib P et al.; An understanding of the complex interactions between pathogenic microbes and their host must include the identification of gene expression patterns during infection . To detect the activation of virulence genes in the opportunistic fungal pathogen Candida albicans in vivo by host signals, we devised a reporter system that is based on FLP-mediated genetic recombination . The FLP gene, encoding the site-specific recombinase FLP, was genetically modified for expression in C . albicans and fused to the promoter of the SAP2 gene that codes for one of the secreted aspartic proteinases, which are putative virulence factors of C . albicans . The SAP2P-FLP fusion was integrated into one of the SAP2 alleles in a strain that contained a deletable marker that conferred resistance to mycophenolic acid and was flanked by direct repeats of the FLP recognition target (FRT) . Using this reporter system, a transient gene induction could be monitored at the level of single cells by the mycophenolic acid-sensitive phenotype of the colonies generated from such cells after FLP-mediated marker excision . In two mouse models of disseminated candidiasis, SAP2 expression was not observed in the initial phase of infection, but the SAP2 gene was strongly induced after dissemination into deep organs . In contrast, in a mouse model of oesophageal candidiasis in which dissemination into internal organs did not occur, no SAP2 expression was detected at any time . Our results support a role of the SAP2 gene in the late stages of an infection, after fungal spread into deep tissue . This new in vivo expression technology (IVET) for a human fungal pathogen allows the detection of virulence gene induction at different stages of an infection, and therefore provides clues about the role of these genes in the disease process. Immunopharmacol Immunotoxicol, 1999 May, 21(2), 331 - 42 Protection of immunosuppressed mice from lethal Candida infection by oral administration of a kampo medicine, hochu-ekki-to; Abe S et al.; The protective effect of a Kampo medicine, Hochu-ekki-to (TJ-41) on experimental candidiasis in immunosuppressed mice was investigated . ICR mice were immunosuppressed by injection of prednisolone or cyclophosphamide, given TJ-41 orally and challenged intravenously with Candida albicans (day 0) . Treatments with a daily dose of 1 g/kg/day of TJ-41 for 8 days from day-4 or for 4 days from day 0 significantly prolonged the life span of the Candida-infected mice pretreated with prednisolone . The latter treatment appeared to inhibit the colonization of Candida in kidneys of the infected mice . These results suggest that Hochu-ekki-to can be used as a therapeutic agent against candidiasis in patients with glucocorticoid-induced immunosuppression. Yeast, 1999 Apr, 15(6), 507 - 11 Heterologous URA3MX cassettes for gene replacement in Saccharomyces cerevisiae; Goldstein AL et al.; Heterologous gene replacement cassettes are powerful tools for dissecting gene function in Saccharomyces cerevisiae . Their primary advantages over homologous gene replacement cassettes include reduced gene conversion (leading to efficient site-specific integration of the cassette) and greater independence of strain background . Perhaps the most widely used cassettes are the MX cassettes containing the dominant selectable kanamycin resistance gene (kanr), which confers resistance to G418 (Wach et al., 1994) . One limitation of the kanMX cassettes is that they are not counterselectable and therefore not readily recyclable, which is important when constructing strains with more than one gene deletion . To address this limitation, and to expand the choices of heterologous markers, we have created two new MX cassettes by replacing the kanr ORF from plasmids pFA6-kanMX3 and pFA6-kanMX4 with the Candida albicans URA3 ORF . These plasmids, pAG60 (CaURA3MX4) and pAG61 (CaURA3MX3) are identical to the kanMX cassettes in all other respects but have the added advantage of being counterselectable and therefore readily recyclable in S . cerevisiae. Drug Discov Today, 1999 Jan, 4(1), 17 - 26 Computer-aided target selection-prioritizing targets for antifungal drug discovery; Spaltmann F et al.; The entire DNA sequence of the Saccharomyces cerevisiae genome was completed in 1996 and represents the first entirely decoded eukaryotic genome . Because major human pathogenic fungi such as Candida albicans are closely related to S . cerevisiae on a molecular level, the question arises as to how this new information can be used to identify and prioritize those genes that are most suitable as targets for antimycotic drug discovery . To tackle this challenge, a software tool called CATS (computer-aided target selection) was developed . The authors describe how it allows an automated and periodically updated assessment of all S . cerevisiae genes to be carried out with regard to their suitability as antifungal targets. Nippon Ishinkin Gakkai Zasshi, 1999, 40(2), 79 - 83 {Fungi and atopic dermatitis}; Hiruma M et al.; Attention has recently been centered on fungi as aggravating factors of atopic dermatitis (AD) due to the frequent detection of IgE antibodies to fungi in patients with severe AD and to positive response of some cases of AD to antifungal therapy . Malassezia sp.: In AD patients with prominent symptoms in the head and neck, areas prone to colonization by Malassezia, the titers of specific anti-Malassezia IgE antibodies are high, which positively correlate with the total IgE value and the severity of AD . The patch test against Malassezia antigens is positive . The rate of isolation of Malassezia from the skin of AD patients is higher than that from the skin of healthy control subjects . Candida sp.: In patients with severe AD, the rate of positive skin prick tests for Candida is high, and a correlation exists between positive skin prick test results and the presence of Candida albicans in nasopharynx . However, the reactivity to Candida antigens in the patch tests is reduced, and a negative correlation is seen . There is no difference between the isolation rate of C . albicans from patients with adult-type AD and normal controls . However, AD patients give a significantly greater number of separate colonies . The range of efficacy rate of antifungal therapy of AD is reported to be 50-65 % . The efficacy rate of our own trial falls within this range . Following treatment, the rate of isolation of fungi decrease significantly, and the titers of specific antifungal IgE antibodies are not statistically significant . The clearance of fungi from the tissue following antifungal therapy probably results in the suppression of direct or indirect inflammatory reaction caused by the fungi . We therefore consider antifungal therapy as one of the second-line therapies to be administered in AD cases resistant to conventional basic therapy. Arch Pharm Res, 1999 Apr, 22(2), 143 - 50 Phototoxicity of melatonin; Kim YO et al.; Melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland . The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracene (positive control) and sodium lauryl sulfate (SLS, negative control) were performed . The methods employed include both in vitro tests such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig . UV absorption spectra and 1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/cm2), but IR spectra of MLT were not changed . The fifty percent inhibitor concentration (IC50) ratio (UV-/UV+) of MLT was 10 . The inhibition zone of irradiated-paper disks treated with MLT was not observed . According to the results of histopathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, hemorrhage and vasodilation in dermis were observed in the irradiated group . These results indicate that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted. J Infect Dis, 1999 Jun, 179(6), 1477 - 84 Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis; Han Y et al.; Candida albicans mannan extracts encapsulated in liposomes were previously used to stimulate mice to produce antibodies protective against candidiasis . In the present study, mannan-protein conjugates without liposomes were tested as vaccine candidates . Mannan extracts were coupled to bovine serum albumin, and isolated conjugates consisted of carbohydrate and protein at a ratio of 0.7-1.0 . Vaccination of mice with the conjugate and an adjuvant yielded antiserum that contained Candida agglutinins . Vaccinated mice challenged with yeast cells had a mean survival time of 56 days, compared with <13 days for control groups . The antiserum protected naive animals against disseminated disease . Naive mice given the antiserum intravaginally developed 79% fewer fungal colony-forming units, compared with control groups . The serum-protective factor was stable at 56 degrees C and was removed by adsorption with yeast cells . It is concluded that the conjugate vaccine can induce protective antibody responses against experimental disseminated candidiasis and Candida vaginal infection. EMBO J, 1999 May 4, 18(9), 2580 - 92 Phenotypic switching in Candida albicans is controlled by a SIR2 gene; Perez-Martin J et al.; We report the cloning of a gene from the human fungal pathogen Candida albicans with sequence and functional similarity to the Saccharomyces cerevisiae SIR2 gene . Deletion of the gene in C . albicans produces a dramatic phenotype: variant colony morphologies arise at frequencies as high as 1 in 10 . The morphologies resemble those described previously as part of a phenotypic switching system proposed to contribute to pathogenesis . Deletion of SIR2 also produces a high frequency of karyotypic changes . These and other results are consistent with a model whereby Sir2 controls phenotypic switching and chromosome stability in C.albicans by organizing chromatin structure. FEMS Microbiol Lett, 1999 Apr 15, 173(2), 475 - 81 Membrane fluidity affects functions of Cdr1p, a multidrug ABC transporter of Candida albicans; Smriti et al.; Earlier, we have shown that the overexpression of an ABC transporter, CDR1, is involved in the emergence of multidrug resistance in Candida albicans . In this study, we checked its function in vivo by expressing it in different isogenic Saccharomyces cerevisiae erg mutants, which accumulated various intermediates of the ergosterol biosynthesis and thus altered the membrane fluidity . Functions like the accumulation of rhodamine 123, beta-estradiol, fluconazole and floppase activity associated with Cdr1p were measured to ascertain their responses to an altered membrane phase . The floppase activity appeared to be favoured by an enhanced membrane fluidity, while the effluxing of substrates and Cdr1p's ability to confer multidrug resistance were significantly reduced . We demonstrate that only some of the functions of Cdr1p were affected by an altered lipid environment. Infect Immun, 1999 May, 67(5), 2482 - 90 In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis; Naglik JR et al.; Secreted aspartyl proteinases are putative virulence factors in Candida infections . Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced . Although the expression of the SAP genes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection . We have developed a reliable and sensitive procedure to detect C . albicans mRNA from whole saliva of patients with oral C . albicans infection and those with asymptomatic Candida carriage . The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C . albicans during colonization and infection of the oral cavity . SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects . SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis . SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples . All seven SAP genes were simultaneously expressed in some patients with oral candidiasis . This is the first detailed study showing that the SAP gene family is expressed by C . albicans during colonization and infection in humans and that C . albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of oral candidiasis. J Physiol Biochem, 1998 Dec, 54(4), 203 - 15 Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders; Castilla-Cortazar I et al.; To assess cell-mediated immunity in depression and anxiety disorders and to elucidate whether immunodysfunction might be related to a high opioid activity, a prospective study of patients with major depression (n = 34) or anxiety disorders (n = 21) was performed . Cellular immunity tests, the in vitro effects of naloxone on monocytes, and beta-endorphin plasma levels were investigated . Peripheral blood mononuclear cells and some monocyte parameters were determined by flow cytometry . Natural killer (NK) cell activity was studied by cytotoxicity, gamma-interferon production by a standard bioassay, monocytic phagocytosis by ingestion of Candida albicans and latex, and blastogenesis by stimulation with phytohaemaglutinin . In major depression and anxiety: 1) a marked reduction in the number of monocytes that ingested particles and expressed cytoskeletal intermediate filaments and surface structures (CR1 receptors and HLA-DR antigens); 2) a monocytosis that was not able to normalize the count of functioning monocytes; 3) an in vitro correction of the monocyte dysfunction by naloxone; 4) a decrease in NK cell number and activity; and 6) an anergy to candidin and tuberculin and a diminished lectin-induced blastogenesis were observed . Some of these immune changes correlated closely with plasma beta-endorphin abnormally high in all the cases . In conclusion, a naloxone-reversible monocyte dysfunction, associated to decreased NK activity and cell-mediated hypersensitivity, was found together with high of beta-endorphin plasma levels . In addition, results suggest that these immunological alterations may be useful in the clinical management of patients with these psychiatric diseases. FEMS Immunol Med Microbiol, 1999 Apr, 23(4), 343 - 54 Characterization of Candida albicans antigenic determinants by two-dimensional polyacrylamide gel electrophoresis and enhanced chemiluminescence; Barea PL et al.; The use of a two-dimensional polyacrylamide gel electrophoresis joined with Western blotting allowed us to investigate the reactivities of antibodies present in sera from mice and humans to antigens of Candida albicans blastoconidia . The analysis of the antibody response in the two models studied and the comparison between the antibody response in infected and noninfected individuals showed that the infection by C . albicans produces changes in the antibody response which may be of relevance in the serodiagnosis of invasive candidiasis . These changes include the induction of antibodies against new antigens, the disappearance of antibodies against a group of antigens and variations in the reactivity of antibodies directed to a different group of antigens . The technique used resolved the isoforms of several antigens including enolase . It is concluded that the antibody response in humans and mice with candidiasis is not homogeneously directed to all the isoforms of an antigen. FEMS Immunol Med Microbiol, 1999 Apr, 23(4), 289 - 93 An investigation into the antimicrobial effects of adrenomedullin on members of the skin, oral, respiratory tract and gut microflora; Allaker RP et al.; Adrenomedullin, a novel vasoactive peptide, is known to be expressed by many surface epithelial cells and it was postulated that this peptide may have a protective role . The objective of the study was to assess the antimicrobial activity of adrenomedullin against members of the human skin, oral, respiratory tract and gut microflora using disc diffusion and broth microdilution assays . All strains of bacteria screened in an agar diffusion assay were sensitive; gram-positive and gram-negative bacteria were equally susceptible . No activity against the yeast Candida albicans was observed . In a broth microdilution assay, minimum inhibitory and minimum bacteriocidal concentrations ranged from 7.75 x 10(-1) to 12.5 microg ml(-1) and 0.003 to > 25.0 microg ml(-1), respectively . We propose an antimicrobial role for adrenomedullin . participating in the prevention of local infection, thus contributing to host defence systems. FASEB J, 1999 May, 13(8), 823 - 32 Disruption of filamentous actin inhibits human macrophage fusion; DeFife KM et al.; The foreign body reaction to implanted biomaterials, characterized by the presence of macrophages and foreign body giant cells (FBGC), can result in structural and functional failure of the implant . Recently, we have shown that interleukin-4 and interleukin-13 can independently induce human macrophage fusion to form FBGC via a macrophage mannose receptor (MR) -mediated pathway . The MR is believed to mediate both endocytosis of glycoproteins and phagocytosis of microorganisms, which bear terminal mannose, fucose, N-acetylglucosamine, or glucose residues . Polarization of microfilaments to closely apposed macrophage membranes as observed with fluorescence confocal microscopy led us to ask whether MR-mediated fusion occurred via a filamentous actin-dependent pathway . Cytochalasins B and D and latrunculin-A, agents that disrupt microfilaments, inhibited macrophage fusion in a concentration-dependent manner . The concentrations of cytochalasins D and B that inhibited fusion did not significantly decrease macrophage adhesion, spreading, or motility but did inhibit internalization of Candida albicans during interleukin-13-enhanced, MR-mediated phagocytosis . Very low concentrations of cytochalasin B (< 2 microM) induced a slight enhancement of macrophage fusion . Taken together, the results of this study suggest that cytokine-induced, MR-mediated macrophage fusion requires an intact F-actin cytoskeleton and that the mechanism of fusion is similar to phagocytosis.--DeFife, K . M., Jenney, C . R., Colton, E., Anderson, J . M . Disruption of filamentous actin inhibits human macrophage fusion. Antimicrob Agents Chemother, 1999 May, 43(5), 1163 - 9 Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450; Asai K et al.; The sterol 14-demethylase P450 (CYP51) of a fluconazole-resistant isolate of Candida albicans, DUMC136, showed reduced susceptibility to this azole but with little change in its catalytic activity . Twelve nucleotide substitutions, resulting in four amino acid changes, were identified in the DUMC136 CYP51 gene in comparison with a reported CYP51 sequence from a wild-type, fluconazole-susceptible C . albicans strain . Seven of these substitutions, including all of those causing amino acid changes, were located within a region covering one of the putative substrate recognition sites of the enzyme (SRS-1) . Polymorphisms within this region were observed in several C . albicans isolates, and some were found to be CYP51 heterozygotes . Among the amino acid changes occurring in this region, only an alteration of Y132 was common among these fluconazole-resistant isolates, which suggests the importance of this residue to the fluconazole resistance of the target enzyme . DUMC136 and another fluconazole-resistant isolate were homozygotes with respect to CYP51, although the typical wild-type, fluconazole-susceptible C . albicans was a CYP51 heterozygote . These findings suggest that part of the fluconazole-resistant phenotype of C . albicans DUMC136 was acquired through a mutation-prone area of CYP51, an area which might promote the formation of fluconazole-resistant CYP51, along with a mechanism(s) which allows the formation of a homozygote of this altered CYP51 in this diploid pathogenic yeast. Antimicrob Agents Chemother, 1999 May, 43(5), 1034 - 41 Assessment of the effect of amphotericin B on the vitality of Candida albicans; Liao RS et al.; The processes involved in cell death are complex, and individual techniques measure specific fractions of the total population . The interaction of Candida albicans with amphotericin B was measured with fluorescent probes with different cellular affinities . These were used to provide qualitative and quantitative information of physiological parameters which contribute to fungal cell viability . SYBR Green I and 5,(6)-carboxyfluorescein were used to assess membrane integrity, and bis-(1,3-dibutylbarbituric acid)trimethine oxonol and 3,3-dihexyloxacarbocyanine iodide were used to evaluate alterations in membrane potential . The fluorescent indicators were compared with replication competency, the conventional indicator of viability . By using these tools, the evaluation of the response of C . albicans to amphotericin B time-kill curves delineated four categories which may represent a continuum between alive and dead . The data showed that replication competency (CFU per milliliter) as determined by conventional antifungal susceptibility techniques provided only an estimate of inhibition . Interpretation of fluorescent staining characteristics indicated that C . albicans cells which were replication incompetent after exposure to greater than 0.5 microgram of amphotericin B per ml still maintained degrees of physiological function. J Antimicrob Chemother, 1999 Mar, 43(3), 419 - 22 Non-albicans oral candidosis in HIV-positive patients; Cartledge JD et al.; Specimens from HIV-positive patients with oral candidosis were taken for culture, species identification and azole susceptibility testing, which was correlated with treatment outcome . Of 921 specimens, 95 yielded non-albicans species, mainly from patients with low CD4 lymphocyte counts and extensive previous azole exposure . Most non-albicans isolates were from specimens co-infected with Candida albicans, complicating the interpretation of in-vitro susceptibility results, which accurately predicted antifungal failure when the non-albicans species was isolated alone . Eighty-five non-albicans isolates were resistant to fluconazole in vitro . Of 149 courses of azole therapy prescribed, 115 failed to clear non-albicans candidosis clinically . Culture media that discoloured in the presence of non-albicans colonies might, therefore, guide therapy. J Antimicrob Chemother, 1999 Mar, 43(3), 411 - 3 Comparisons of the effects of fungicidal and fungistatic antifungal agents on the morphogenetic transformation of Candida albicans; Hawser S et al.; Eleven different antifungal agents were compared, and their ability to inhibit the morphogenetic transformation of Candida albicans was examined together with their ability to inhibit growth, as measured by MIC methodology . The fungicidal potential of each agent was also determined . Of the antifungal agents tested, only amphotericin B, mulundocandin and aculeacin inhibited the transformation at sub-MIC values; all three agents showed fungicidal activity at concentrations close to the MIC . All other agents were fungicidal only at concentrations much higher than the MIC and inhibited the morphogenetic transformation only at concentrations above the MIC . These data suggest that fungicidal antifungal agents are more likely to act by inhibiting the morphogenetic transformation of C . albicans while fungistatic agents are unable to do so and are more likely to block growth by budding. Jpn J Antibiot, 1999 Feb, 52(2), 146 - 52 {The in vitro properties of a new hydroxypyridone antimycotic rilopirox, with special reference to its anti-Candida activity}; Harada I et al.; In vitro properties of a new hydroxypyridone antimycotic rilopirox (RIL) with special reference to its anti-Candida activities were studied in comparison with the three reference drugs, ciclopirox olamine (CPO), oxiconazole nitrate (OCZ) and isoconazole nitrate (ICZ), using several strains of Candida albicans and Candida glabrata as the test organisms . RIL was potently fungicidal for growing cultures of these Candida strains, whereas all the three reference drugs were slightly fungicidal or fungistatic . Unlike OCZ and ICZ whose anti-Candida activity was decreased by lowering pH or adding serum to culture media, the activity of RIL was scarecely affected by change in pH or serum addition . However, RIL became less potent in the presence of Fe3+ at concentrations of 10(-5) mmol/ml or above . These findings suggest that RIL will be useful as a topical anti-Candida agent. Med Pediatr Oncol, 1999 May, 32(5), 344 - 8 Fungal colonization and infection in children with acute leukemia and lymphoma during induction therapy; Gozdasoglu S et al.; BACKGROUND: Fungal infection represents a growing problem in children with hematologic malignancies . During chemotherapy induced neutropenia, colonization with fungi is considered a major risk factor for subsequent fungal infection . The rates and risk factors for mycotic infections in pediatric oncology patients is undetermined, particularly for centers in developing countries . The aim of this study was to evaluate the rates and risk factors of fungal colonization in children with acute leukemia and lymphoma at one of the major pediatric hematology/oncology centers in Turkey . PROCEDURE: Fifty-two consecutive children newly diagnosed with acute leukemia and lymphoma during intensive remission induction therapy were evaluated for the occurrence of fungal colonization (defined as at least one positive surveillance culture) and infection . RESULTS: Thirty-six of the 52 patients (69.2%) were colonized by Candida albicans which was the only fungus isolated from surveillance cultures . There were three (5.8%) proven systemic fungal infections: two cases of candidemia and one case of brain abscess with Aspergillus spp . isolated from tissue . All patients with fungal colonization were receiving prophylactic or curative antibiotics . No significant association was found between type of disease and fungal colonization, but there was a significant association with neutropenia . CONCLUSIONS: Our findings suggest that there is a high rate of fungal colonization in children receiving remission induction therapy for acute leukemia and lymphoma . Limiting the use of antibiotics and instituting antifungal chemoprophylaxis may decrease the rate, while the early initiation of empiric antifungal therapy in patients with fever and suspected mycotic colonization may increase survival in these patients. FEMS Immunol Med Microbiol, 1999 Mar, 23(3), 229 - 34 Clinical strains of Candida albicans express the surface antigen glyceraldehyde 3-phosphate dehydrogenase in vitro and in infected tissues; Gil ML et al.; We have previously described the presence of an enzymatically active form of glyceraldehyde 3-phosphate-dehydrogenase (GAPDH) in the cell surface of Candida albicans ATCC 26555 which is also a fibronectin and laminin binding protein . Immunohistochemical analysis of tissue sections from patients with disseminated candidiasis with a polyclonal antiserum to GAPDH from C . albicans (PAb anti-CA-GAPDH) revealed that the enzyme is expressed at the surface of fungal cells in infected tissues . The same PAb detected the presence of GAPDH species, with a molecular mass of approximately 33 kDa, in cell wall extracts obtained from clinical isolates of the fungus . These cell surface-bound GAPDH moieties exhibited a dose-dependent dehydrogenase activity . These results indicate that this cell surface-bound GAPDH plays a role during infection probably contributing to the attachment of fungal cells to host tissues. Microbiology, 1999 Mar, 145 ( Pt 3), 695 - 701 Monoclonal antibody 3H8: a useful tool in the diagnosis of candidiasis; Marcilla A et al.; In a previous series of experiments six mAbs were obtained against cell wall extracts of Candida albicans ATCC 26555 . After several studies only one of them, designated 3H8, has been used to produce a commercial kit for the rapid diagnosis of candidiasis, Bichro-latex albicans (Fomouze Diagnostics) . The present study involved the generation and characterization of this mAb as an immunoglobulin G1 which recognizes mannoproteins of high molecular mass present in the C . albicans cell wall . ELISA assays showed that the presence of the epitope recognized by mAb 3H8 was similar in both yeast and mycelial cell walls of C . albicans, in contrast to the epitope for mAb 1B12, which is mainly expressed in the yeast cell wall . The 3H8 epitope was located at the external surface in C . albicans ATCC 26555, whereas it is partially cryptic in the cell wall in other C . albicans strains . No reaction was observed with other Candida species . Immunohistochemical studies using this antibody demonstrated that it specifically recognized C . albicans in tissue, detecting mycelial forms and, to a lesser extent, blastospores, suggesting that it is also a valuable tool in the evaluation of fungal infections in paraffin-embedded tissue, particularly when identification is required. Microbiology, 1999 Mar, 145 ( Pt 3), 689 - 94 Characterization of a haemolytic factor from Candida albicans; Watanabe T et al.; The culture supernatant of Candida albicans promoted the disruption of human red blood cells (RBCs) . The haemolytic activity was detected in a sugar-rich fraction (about 200 kDa) from Sephacryl S-100 chromatography . As the haemolytic activity was adsorbed by concanavalin A-Sepharose, the haemolytic factor may be a mannoprotein . The activity was inactivated by periodate oxidation, indicating that the sugar moiety of the mannoprotein played an important role in the haemolysis . The structure of the sugar moiety of the mannoprotein was identified as a cell-wall mannan by 1H-NMR analysis, and purified C . albicans mannan promoted the disruption of RBCs . The binding of mannan to RBCs was demonstrated by flow cytometric analysis and was inhibited by the addition of band 3 protein inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) . The haemolysis caused by mannan was inhibited by DIDS, SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid) and bis(sulfosuccinimidyl) suberate, but not by pyridoxal 5-phosphate . These results indicated that a mannoprotein released from C . albicans bound to the band 3 protein on RBCs, thereby promoting their disruption. Biochim Biophys Acta, 1999 Apr 19, 1427(2), 245 - 55 Copper- and zinc-containing superoxide dismutase and its gene from Candida albicans; Hwang CS et al.; Cytosolic copper- and zinc-containing superoxide dismutase was purified 136-fold with an overall yield of 2.5% to apparent electrophoretic homogeneity from the dimorphic pathogenic fungus, Candida albicans . The molecular mass of the native enzyme was 39.4 kDa and the enzyme was composed of two identical subunits with a molecular mass of 19.6 kDa . The enzyme was stable in the range of pH 4.0-9.0 and up to 55 degrees C . The ultraviolet-visible absorption spectrum of the enzyme showed the absorption band of copper- and zinc-containing superoxide dismutase at 660 nm . The atomic absorption analysis revealed that the enzyme contained 0.87 g-atom of copper and 0.79 g-atom of zinc per mole of subunit . The N-terminal amino acid sequence alignments up to the 40th residue showed that copper- and zinc-containing superoxide dismutase from C . albicans has high similarity to other eukaryotic copper- and zinc-containing superoxide dismutases . The sod1 encoding copper- and zinc-containing superoxide dismutase has been cloned using a polymerase chain reaction fragment as a probe . Sequence analysis of the sod1 predicted a copper- and zinc-containing superoxide dismutase that contains 154 amino acids with a molecular mass of 16143 Da and displayed 79%, 69%, and 57% sequence identity to the homologues of Neurospora crassa, Saccharomyces cerevisiae, and bovine, respectively . The cloned sod1 contained an intron of 245 nucleotides, which was verified by reverse transcription-polymerase chain reaction. Retina, 1999, 19(2), 122 - 6 In vitro antimicrobial activity of silicone oil against endophthalmitis-causing agents; Ozdamar A et al.; PURPOSE: To investigate the antimicrobial activity of silicone oil against endophthalmitis-causing agents in vitro . METHODS: The antimicrobial activity of silicone oil was tested on Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus spp . The bacteria and fungi were separately inoculated into 1,300 centistokes silicone oil . Control inoculations were done in two different media: physiologic saline and brain-heart infusion (BHI) for bacteria and Sabouraud broth and physiologic saline for fungi . From each medium, 0.001-mL samples were taken and plated in Petri dishes . After overnight incubation, colony-forming units (CFUs) were enumerated . Culturing from the initially prepared specimens, incubating overnight, and counting CFUs was repeated until no growth of microorganisms was seen in the silicone oil-containing media . Macroscopic photography of the colonies and light microscopic photography of microorganisms were performed . RESULTS: All the microorganisms showed an apparent decrease in CFUs, with elimination between 7 and 21 days in silicone oil . Colony-forming units of microorganisms remained stable in physiologic saline during the study, with the exception of gradual decrease in CFUs of S . aureus and S . epidermidis from the beginning of the third day . In BHI and Sabouraud broth, both bacteria and fungi showed a growth pattern that was compatible with the growth curve of microorganisms . CONCLUSION: Silicone oil has an antimicrobial activity against S . aureus, S . epidermidis, P . aeruginosa, C . albicans, and Aspergillus spp., which are common endophthalmitis-causing agents. Diagn Microbiol Infect Dis, 1999 Apr, 33(4), 231 - 9 Evaluation of DNA-based typing procedures for strain categorization of Candida spp; Espinel-Ingroff A et al.; DNA-based procedures have replaced earlier epidemiologic methodologies that relied on nonreproducible and insensitive measurements of phenotypic characteristics to identify a specific strain as the source of infection . The reliability (interlaboratory percent agreement for strain delineation) and sensitivity (recognition of subtle strain-to-strain variation) of similar DNA-based typing systems by different laboratories were evaluated . Ten isolates (five epidemiologic-related and five unrelated strains each) of Candida albicans, C . lusitaniae, C . parapsilosis, C . tropicalis, and Candida (Torulopsis) glabrata were characterized in a blinded fashion by three laboratories . All 50 isolates were subtyped in each laboratory by electrophoretic karyotyping (EK) analysis using contour-clamped homogenous electric field (CHEF) electrophoresis protocols . In addition, two laboratories also performed restriction endonuclease analysis of genomic DNA (REAG) using the restriction endonucleases SfiI and BssHII followed by CHEF electrophoresis separation of resulting fragments . DNA strain identification of the 50 isolates by the three different laboratories using similar CHEF methodologies demonstrated the following species-dependent, interlaboratory reproducibility: C . tropicalis (82%), C . parapsilosis (83%), C . albicans (90%), C . lusitaniae (93%), and C . glabrata (100%) . In addition, agreement was higher by the CHEF method (83 to 100%), when compared with the strain types identified by the REAG (60 to 100%) method . Five to seven strains of each Candida species evaluated were detected by the different methodologies used for this study . This study indicates that these procedures are relatively discriminatory and reliable tools to study strain-to-strain variations in epidemiologic evaluations of these yeasts. Chem Pharm Bull (Tokyo), 1999 Mar, 47(3), 351 - 9 Optically active antifungal azoles . VIII . Synthesis and antifungal activity of 1-{(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl}- 3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones; Kitazaki T et al.; New optically active antifungal azoles, 1-{(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl }-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1,2) and 2-imidazolidinones (3,4), were prepared in a stereocontrolled manner from (1S)-1-{(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxiranyl}ethanols (15, 16) . Compounds 1-4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro . Furthermore, the imidazolidinones, 3b--e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus. Berl Munch Tierarztl Wochenschr, 1999 Mar, 112(3), 104 - 7 {Fungal flora in chicken stalls and its etiopathogenic importance for humans and animals}; Vissiennon T; In order to find out the mycoflora prevailing in chicken pens, and to appreciate the health hazards for employees (incl . veterinarians) and animals, twenty litter samples and 6 sedimented dust trials were analysed mycologically . The following results were found: Bedding and dust samples all contained between 3.57 and 1.30 x 10(7) c.f.u./g DW . The commonest fungus is A . fumigatus with 3.41 x 10(4) - 1.30 x 10(7) c.f.u./g DW in bedding and 2.70 x 10(5) - 3.30 x 10(6) c.f.u./g DW in sedimented dust . In addition, the following fungal spp . were detected (in c.f.u./g DW): Scopulariopsis brevicaulis (3.57 x 10(3) - 6.50 x 10(7)), Pseudallescheria boydii (2.70 x 10(6)), A . flavus group (up to 8.41 x 10(5)), A . clavatus (6.00 x 10(5)), Candida albicans (4.88 x 10(5)), Alternaria spp . (4.49 x 10(5)), Penicillium spp . (up to 1.06 x 10(5)), A . terreus (8.47 x 10(4)), A . versicolor group (up to 8.44 x 10(4)), A . niger (5.93 x 10(4)), Aureobasidium sp . (3.96 x 10(3)), Mucor circinelloides (3.42 x 10(3)), Phialophora sp . (1.30 x 10(3)), C . pseudoiropicalis (4.04 x 10(2)), A . nidulans (3.90 x 10(2)), Acremonium sp . (3.55 x 10(2)), M . racemosus (1.19 x 10(2)) . Negligible was the detected level of Chrysosporium pannorum (84.10), Rhizomucor pusillus (81.00), Beauveria alba (59.60), C . tropicalis (40.40), Trichoderma sp . (4.70), A . flavipes (4.38) . Dermatophytes were not found . The fungal spectrum was broader in the dust than in litter samples. Biochim Biophys Acta, 1999 Apr 12, 1431(1), 107 - 19 Candidacidal activity prompted by N-terminus histatin-like domain of human salivary mucin (MUC7)1; Gururaja TL et al.; Histidine-rich peptides (histatins, Hsn) in saliva are thought to provide a non-immune defense against Candida albicans . Sequence homology search of the human salivary mucin, MUC7, against histatins revealed a domain at the N-terminus (R3-Q17) having 53% identity to Hsn-5 . To determine its candidacidal activity, this 15 residue basic histidine-rich domain of MUC7 (I) was prepared by solid-phase Fmoc chemistry . Various N- and C-terminal protected derivatives of I were also synthesized to correlate the effect of peptide overall charge in exhibiting cidal potency . Candidacidal activity measurement of I and its variants showed considerable ED50 values (effective dosage required to kill 50% of candida cells), albeit greater than Hsn-5 (ED50 approximately 4-6 microM) . Of the various analogs tested, N-terminal free acid (I, ED50 approximately 40 microM) and amide (V, ED50 approximately 16 microM) exhibited appreciable candidacidal activities suggesting the possible role of peptide net charge in cidal action . Blocking of N-terminus with a bulky octanoyl group showed only marginal effect on the cidal activity of I or V, indicating that hydrophobicity of these synthetic constructs may not be important for exerting such activities . Membrane-induced conformational transition from random coil to helical structures of all the test peptides implied their tendency to adapt order structures at the lipid-membrane interface similar to that of Hsn-5 . However, comparison of propensity for helical structure formation vs . ED50 indicated that cidal potency of MUC7 Hsn-like peptides depends largely on electrostatic interactions irrespective of secondary structural elements . Delineation of solution structure of the most active peptide (V) by 2D-NMR revealed essentially a non-structured conformation in aqueous medium, which further supported the fact that the peptide helical structure may not be a prerequisite for posing candidacidal activity . The formation of smaller truncated peptides and/or Hsn-like fragments on proteolytic degradation of intact MUC7 in the presence of oral flora provided indirect evidence that mucin could serve as a backup candidacidal agent to salivary Hsn. J Comp Pathol, 1999 May, 120(4), 369 - 81 Inhibition of phagosome-lysosome fusion in ovine polymorphonuclear leucocytes by Ehrlichia (Cytoecetes) phagocytophila; Gokce HI et al.; Ehrlichia (Cytoecetes) phagocytophila, the causative agent of tick-borne fever, is an intracellular bacterium that survives and multiplies within granulocytes and monocytes . In the present study, the possible fusion of lysosomes with phagosomes containing E . phagocytophila was investigated in poly-morphonuclear (PMN) cells of sheep infected with the agent, acid phosphatase cytochemistry and cationized ferritin being used as markers of primary and secondary lysosomal enzymes . Latex beads or Candida albicans were incubated with infected and uninfected PMN cells and labelled with the same lysosomal markers . Lysosomal enzymes labelled with the markers were commonly found in phagosomes containing latex beads or C . albicans, but there was no evidence of phagosome-lysosome (P-L) fusion in phagosomes containing E . phagocytophila . It was significant that in cells that contained E . phagocytophila, latex beads and C . albicans, P-L fusion occurred only in phagosomes containing latex beads or C . albicans . However, evidence of P-L fusion with phagosomes containing E . phagocytophila was obtained when PMN cells were incubated with oxytetracycline, which is known to inhibit synthesis of bacterial proteins . These findings indicate that E . phagocytophila is capable of inhibiting P-L fusion and that oxytetracycline depresses this capability . Yeast, 1999 Mar 15, 15(4), 323 - 7 Isolation and sequence of the GCR3 homologue from Candida albicans by complementation of (delta)gcr3 strain of Saccharomyces cerevisiae; Uemura H et al.; To study the function of GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, a Candida albicans gene which complements the growth defect of the (delta)gcr3 mutant was isolated . Transformants of this gene also recovered the glycolytic enzyme activities . Its DNA sequencing predicted an 886 amino acid protein with 30.4% identity to the Gcr3p of S . cerevisiae. Eur J Pediatr, 1999 Apr, 158(4), 275 - 80 Fungal endocarditis in critically ill children; Aspesberro F et al.; All cases of infective endocarditis occurring from January 1990 to December 1996 at our institution were reviewed, with a special focus on fungal endocarditis . Five critically ill children with fungal endocarditis and eleven children with bacterial endocarditis were recorded . The proportion of fungal endocarditis in our series was 5/16 (31%) and Candida albicans (4/5) was the most common fungal pathogen . Only one patient required heart surgery because of a loose patch but all the others were treated only by medical management for cure . The hospital survival rate was 80% (4/5) and the overall long-term survival rate was 60% (3/5) with only one death directly related to fungal infection . CONCLUSION: Despite the small number of cases, a sole medical approach including amphotericin B and long-term fluconazole prophylaxis for the treatment of fungal endocarditis in critically ill children seems to offer an alternative to surgical treatment which may be kept for failure of medical treatment. J Clin Microbiol, 1999 May, 37(5), 1464 - 8 Coaggregation of Candida dubliniensis with Fusobacterium nucleatum; Jabra-Rizk MA et al.; The binding of microorganisms to each other and oral surfaces contributes to the progression of microbial infections in the oral cavity . Candida dubliniensis, a newly characterized species, has been identified in human immunodeficiency virus-seropositive patients and other immunocompromised individuals . C . dubliniensis phenotypically resembles Candida albicans in many respects yet can be identified and differentiated as a unique Candida species by phenotypic and genetic profiles . The purpose of this study was to determine oral coaggregation (CoAg) partners of C . dubliniensis and to compare these findings with CoAg of C . albicans under the same environmental conditions . Fifteen isolates of C . dubliniensis and 40 isolates of C . albicans were tested for their ability to coaggregate with strains of Fusobacterium nucleatum, Peptostreptococcus micros, Peptostreptococcus magnus, Peptostreptococcus anaerobius, Porphyromonas gingivalis, and Prevotella intermedia . When C . dubliniensis and C . albicans strains were grown at 37 degrees C on Sabouraud dextrose agar, only C . dubliniensis strains coaggregated with F . nucleatum ATCC 49256 and no C . albicans strains showed CoAg . However, when the C . dubliniensis and C . albicans strains were grown at 25 or 45 degrees C, both C . dubliniensis and C . albicans strains demonstrated CoAg with F . nucleatum . Heating the C . albicans strains (grown at 37 degrees C) at 85 degrees C for 30 min or treating them with dithiothreitol allowed the C . albicans strains grown at 37 degrees C to coaggregate with F . nucleatum . CoAg at all growth temperatures was inhibited by mannose and alpha-methyl mannoside but not by EDTA or arginine . The CoAg reaction between F . nucleatum and the Candida species involved a heat-labile component on F . nucleatum and a mannan-containing heat-stable receptor on the Candida species . The CoAg reactions between F . nucleatum and the Candida species may be important in the colonization of the yeast in the oral cavity, and the CoAg of C . dubliniensis by F . nucleatum when grown at 37 degrees C provides a rapid, specific, and inexpensive means to differentiate C . dubliniensis from C . albicans isolates in the clinical laboratory. Biochem Mol Biol Int, 1999 Mar, 47(3), 369 - 76 Structural characteristics of tenecin 3, an insect antifungal protein; Lee YT et al.; Tenecin 3, an antifungal protein, previously isolated from the insect Tenebrio molitor, inhibits growth of the fungus Candida albicans . However, the antifungal mechanism and functions of tenecin 3 remain unknown . As an initial step to study the mechanism and functions, physical and structural properties of tenecin 3 were examined by circular dichroism (CD) analysis and 2D nuclear overhauser effect spectroscopy . These analyses suggest that tenecin 3 has a propensity of random structure with very loose turn-like elements . The CD results also indicate that this random structural propensity is not significantly affected by temperature, pH, and by the presence of organic solvents or sodium dodecyl sulfate (SDS) micelles . However, the hydrodynamic studies suggest that tenecin 3 is not in extended form in spite of its random structural feature. J Clin Microbiol, 1999 May, 37(5), 1587 - 90 Rapid PCR test for discriminating between Candida albicans and Candida dubliniensis isolates using primers derived from the pH-regulated PHR1 and PHR2 genes of C . albicans; Kurzai O et al.; The development of a satisfactory means to reliably distinguish between the two closely related species Candida albicans and Candida dubliniensis in the clinical mycology laboratory has proved difficult because these two species are phenotypically so similar . In this study, we have detected homologues of the pH-regulated C . albicans PHR1 and PHR2 genes in C . dubliniensis . Restriction fragment length polymorphism analysis suggests that there are significant sequence differences between the genes of the two species . In order to exploit this apparent difference, oligonucleotide primers based on the coding sequence of the C . albicans PHR1 structural gene were designed and used in PCR experiments . Use of these primers with C . albicans template DNA from 17 strains yielded a predicted 1.6-kb product, while C . dubliniensis template DNA from 19 strains yielded no product . We therefore propose that PCR using these primers is a rapid and reliable means of distinguishing the two germ tube- and chlamydospore-producing species C . albicans and C . dubliniensis. J Clin Microbiol, 1999 May, 37(5), 1510 - 7 New enzyme immunoassays for sensitive detection of circulating Candida albicans mannan and antimannan antibodies: useful combined test for diagnosis of systemic candidiasis; Sendid B et al.; Two standardized enzyme immunoassays for the serological diagnosis of candidiasis were developed . The first one detects antimannan antibodies, while the second one detects mannan with a sensitivity of 0.1 ng/ml . These tests were applied to 162 serum samples retrospectively selected from 43 patients with mycologically and clinically proven candidiasis caused by Candida albicans . Forty-three serum samples were positive for mannan, and 63 had significant antibody levels . Strikingly, only five serum samples were simultaneously positive by both tests . When the results were analyzed per patient, 36 (84%) presented at least one serum positive by one test . For 30 of them, positivity by one test was always associated with negative results by the other test for any of the tested sera . For six patients whose sera were positive for either an antigen or an antibody response, a balance between positivity by each test was evidenced by kinetic analysis of sera drawn during the time course of the infection . Controls consisted of 98 serum samples from healthy individuals, 93 serum samples from patients hospitalized in intensive care units, and 39 serum samples from patients with deep mycoses . The sensitivities and specificities were 40 and 98% and 53 and 94% for mannanemia or antibody detection, respectively . These values reached 80 and 93%, respectively, when the results of both tests were combined . These observations, which clearly demonstrate a disparity between circulation of a given mannan catabolite and antimannan antibody response, suggest that use of both enzyme immunoassays may be useful for the routine diagnosis of candidiasis. J Clin Microbiol, 1999 May, 37(5), 1398 - 403 Postsurgical Candida albicans infections associated with an extrinsically contaminated intravenous anesthetic agent; McNeil MM et al.; From 16 to 30 April 1990, four of 364 (1%) postsurgical patients at one hospital developed Candida albicans fungemia or endophthalmitis . The case patients' surgeries were clustered on two days . To identify risk factors for C . albicans infections, we conducted a cohort study comparing these 4 patients with 67 control patients who had surgeries on the same days but did not acquire C . albicans infections . The participation of anesthesiologist 9 (relative risk {RR}, undefined; P < 0.001) and receipt of intravenous propofol, an anesthetic agent without preservative, which was administered by an infusion pump (RR, 8.8; P = 0.048) were identified as risk factors for C . albicans infections . The anesthetic had been recently introduced in the hospital . Hand cultures of 8 of 14 (57%) anesthesiologists were positive for Candida species; one yielded C . albicans . Anesthesiologist 9 was the only one to use stored syringes of propofol in the infusion pump and to reuse propofol syringes . DNA fingerprinting with a digoxigenin-labeled C . albicans repetitive element 2 probe and electrophoretic karyotyping showed two distinct banding patterns among patient isolates . We hypothesize that extrinsic contamination of propofol by anesthesiologist 9 likely resulted in C . albicans infections . These data suggest that strict aseptic techniques must be used when preparing and administering propofol. J Clin Microbiol, 1999 May, 37(5), 1376 - 80 High aspartyl proteinase production and vaginitis in human immunodeficiency virus-infected women; de Bernardis F et al.; Vaginal isolates of Candida albicans from human immunodeficiency virus-positive (HIV+) and HIV- women with or without candidal vaginitis were examined for secretory aspartyl proteinase (Sap) production in vitro and in vivo and for the possible correlation of Sap production with pathology and antimycotic susceptibility in vitro . HIV+ women with candidal vaginitis were infected by strains of C . albicans showing significantly higher levels of Sap, a virulence enzyme, than strains isolated from HIV+, C . albicans carrier subjects and HIV- subjects with vaginitis . The greater production of Sap in vitro was paralleled by greater amounts of Sap in the vaginal fluids of infected subjects . In an estrogen-dependent, rat vaginitis model, a strain of C . albicans producing a high level of Sap that was isolated from an HIV+ woman with vaginitis was more pathogenic than a strain of C . albicans that was isolated primarily from an HIV-, Candida carrier . In the same model, pepstatin A, a strong Sap inhibitor, exerted a strong curative effect on experimental vaginitis . No correlation was found between Sap production and antimycotic susceptibility, as most of the isolates were fully susceptible to fluconazole, itraconazole, and other antimycotics, regardless of their source (subjects infected with strains producing high or low levels of Sap, subjects with vaginitis or carrier subjects, or subjects with or without HIV) . Thus, high Sap production is associated with virulence of C . albicans but not with fungal resistance to fluconazole in HIV-infected subjects, and Sap is a potentially new therapeutic target in candidal vaginitis. J Immunol, 1999 Apr 15, 162(8), 4876 - 81 Soluble murine IL-1 receptor type I induces release of constitutive IL-1 alpha; Netea MG et al.; IL-1 alpha and IL-1 beta are proinflammatory cytokines involved in the pathogenesis of many infectious and noninfectious inflammatory diseases . To reduce IL-1 toxicity, extracellular domains of the soluble (s) IL-1R are shed from cell membranes and prevent triggering of cell-bound receptors . We investigated to what extent murine sIL-1RI can neutralize the IL-1 produced by LPS-stimulated macrophages . When mouse peritoneal macrophages were incubated with LPS, addition of sIL-1RI significantly inhibited the bioactivity of IL-1 . Stimulation of cells with sIL-1RI alone induced no bioactive IL-1 . When immunoreactive cytokine concentrations were measured with specific radioimmunoassays, sIL-1RI alone appeared to induce a significant release of IL-1 alpha in a concentration-dependent manner . This effect was independent of new protein synthesis . The production of IL-1 beta or TNF-alpha was not influenced by sIL-1RI . There was no interference of sIL-1RI with the IL-1 alpha radioimmunoassay . In mice, an i.v . injection of sIL-RI alone induced a rapid release of IL-1 alpha, but not of TNF-alpha or IL-1 beta . Treatment of mice with sIL-1RI improved the survival during a lethal infection with Candida albicans . In conclusion, sIL-1RI induces a rapid release of IL-1 alpha from cells, as well as into the systemic circulation . Although this IL-1 alpha may be inactivated in circulation by the same sIL-1RI, this phenomenon probably has immunostimulatory effects at local levels where the sIL-1RI-induced IL-1 alpha acts in a paracrine or autocrine manner. Med Mycol, 1999 Feb, 37(1), 35 - 41 In vitro susceptibility of Candida species to lactoferrin; Xu YY et al.; Lactoferrin is an antimicrobial protein present in human mucosal secretions as well as saliva . As there is no information on the relative fungicidal activity of human and bovine lactoferrin, an oral isolate of Candida albicans was studied for its susceptibility to these two proteins . Exposure to a concentration of 20 micrograms ml-1 of either HLF or BLF at 37 degrees C inactivated the yeast to the same degree irrespective of the incubation time of 45, 90 or 150 min . A similar study, using 20 micrograms ml-1 BLF and an incubation time of 150 min, elicited varying anticandidal activity against 35 isolates belonging to six different Candida species . Thus, BLF was fungicidal for the six Candida species in the following decreasing order, C . tropicalis > C . krusei > C . albicans > C . guilliermondii > C . parapsilosis > C . glabrata; the latter being the most resistant . These Candida species also demonstrated significant intra-species variation in susceptibility to the protein (P < 0.05) . When the yeast cells exposed to BLF were examined by cryo-scanning electron microscopy, profound cell wall changes such as cell surface blebs, swelling and cell collapse were noted . These findings suggest that lactoferrin, a constituent of saliva, may differentially modulate the carriage of Candida species in the oral cavity. Quintessence Int, 1998 Nov, 29(11), 705 - 10 Candida albicans levels in patients with Sjögren's syndrome before and after long-term use of pilocarpine hydrochloride: a pilot study; Rhodus NL et al.; OBJECTIVE: The purpose of this study was to compare the quantities of oral Candida albicans in patients with primary and secondary Sjogren's syndrome before and after the use of orally administered pilocarpine hydrochloride for 1 year . METHOD AND MATERIALS: Twelve female subjects with primary (n = 4) and secondary (n = 8) Sjogren's syndrome (mean age +/- SEM = 56.7 +/- 5.7 years) were enrolled in the study, after meeting rigid enrollment criteria . Oropharyngeal collection of samples and culturing was performed on each subject . Cultures specific for Candida albicans were plated into a culture media tube using the Oricult kit and also by serial dilutions and plating by a streptomycin-vancomycin technique . Cultures were incubated for 48 hours at 37 degrees C . The subjects used 5 mg of pilocarpine hydrochloride, administered orally three times daily, for 1 year, after which both of the Candida cultures were repeated . None of the subjects used antifungal medications, none smoked, and all were dentate . RESULTS: There was a significant difference in the prevalence of Candida after the use of pilocarpine hydrochloride for both groups . At the start of the study, 75% of all subjects were positive for Candida . Following the use of pilocarpine, 25% had positive cultures . There was also a decrease in the prevalence of clinical manifestations of infection from 75% of subjects to 25% . There was a significant decrease in the numbers of Candida cultured following the use of pilocarpine . CONCLUSION: Long-term administration of pilocarpine hydrochloride resulted in a significant reduction in Candida albicans colonization in patients with primary or secondary Sjogren's syndrome. Yonsei Med J, 1999 Feb, 40(1), 56 - 60 Diagnosis of trichomoniasis by polymerase chain reaction; Ryu JS et al.; The clinical usefulness of polymerase chain reaction (PCR) for the diagnosis of trichomoniasis was evaluated in comparison with other conventional tests . PCR was used for specific detection of Trichomonas vaginalis by primers based on the repetitive sequence cloned from T . vaginalis (TV-E650) . Between June 1996 and August 1997, 426 patients visited the department of obstetrics and gynecology, Hanyang University Kuri Hospital and were examined for trichomoniasis using wet mount examination, Papanicolaou (Pap) smear, culture and PCR . One hundred and seventy-seven patients (group A) visited with the symptoms of vaginal discharge and 249 patients (group B) visited for regular cervical Pap smear with no vaginal symptoms . From group A (n = 177), 3 infections (2.0%) were detected by wet mount, 6 infections (3.3%) by Pap smear and culture, and 17 infections (10.4%) by PCR . From group B (n = 249), 4 patients (1.6%) were found to have T . vaginalis by culture and 6 infections (2.4%) were detected by PCR . Therefore, in both groups, PCR for T . vaginalis showed a higher detection rate compared with conventional wet mount, Pap smear or culture . The detection by PCR was specific for T . vaginalis since no amplification was detected with DNAs from other protozoa and Candida albicans . The sensitivity and specificity of PCR were 100% . This method could detect T . vaginalis in vaginal discharge at a concentration as low as 1 cell per PCR mixture . These results indicate that PCR could be used as a specific and sensitive diagnostic tool for human trichomoniasis. Int J Prosthodont, 1999 Jan-Feb, 12(1), 83 - 6 Adherence of Candida albicans to the surface of polymethylmethacrylate--E glass fiber composite used in dentures; Waltimo T et al.; PURPOSE: The use of reinforcing fibers in dentures has raised concerns about possible increased adherence of yeasts to the surface . The aim of this in vitro study was to compare the adherence of Candida albicans to the surface of denture-base polymer and to E-glass fibers . MATERIALS AND METHODS: Test specimens were made from an autopolymerized denture-base resin (Palapress) reinforced with preimpregnated unidirectional E-glass fibers, which were exposed at the surface . The test specimens were pretreated with parotid saliva and incubated without agitation in standardized yeast suspensions (10(8) colony-forming units per mL) in phosphate-buffered saline at 37 degrees C for 1 hour . The test specimens were then washed to remove nonadherent cells . After being air dried, they were sputter coated with gold-palladium for scanning electron microscopy (SEM) . To compare the adherence to different surfaces, the number of yeast cells found either on the polymer matrix or on the glass fibers was counted from SEM fields (170 microns x 120 microns, 600 x) of randomly selected areas . RESULTS: The mean density of yeast cell found on the surface of the polymer matrix was significantly higher (P < 0.001) than that on the surface of glass fibers . The number of adherent yeast cells found at the interface between the fibers and polymer matrix was high . CONCLUSION: The adherence of C albicans to E-glass fibers was lower than to polymer matrix in the denture composite . If fibers are exposed only during polishing of the composite, the reinforcing material appears not to increase the adherence of this common oral yeast . However, areas with permanently exposed fibers may provide mechanical retention for yeast cells at the interface of the components. J Appl Microbiol, 1999 Mar, 86(3), 446 - 52 Influence of organic matter, cations and surfactants on the antimicrobial activity of Melaleuca alternifolia (tea tree) oil in vitro; Hammer KA et al.; The effect of some potentially interfering substances and conditions on the antimicrobial activity of Melaleuca alternifolia (tea tree) oil was investigated . Agar and broth dilution methods were used to determine minimum inhibitory and cidal concentrations of tea tree oil in the presence and absence of each potentially interfering substance . Activity was determined against Gram-positive and -negative bacteria, and Candida albicans . Minimum inhibitory or cidal concentrations differed from controls by two or more dilutions, for one or more organisms, where Tween-20, Tween-80, skim-milk powder and bovine serum albumin were assessed . These differences were not seen when assays were performed in anaerobic conditions, or in the presence of calcium and magnesium ions . The effect of organic matter on the antimicrobial activity of tea tree oil was also investigated by an organic soil neutralization test . Organisms were exposed to lethal concentrations of tea tree oil ranging from 1-10% (v/v), in the presence of 1-30% (w/v) dry bakers' yeast . After 10 min contact time, viability was determined . At > or = 1%, organic matter compromised the activity of each concentration of tea tree oil against Staphylococcus aureus and C . albicans . At 10% or more, organic matter compromised the activity of each tea tree oil concentration against Pseudomonas aeruginosa . Organic matter affected 1 and 2% tea tree oil, but not 4 and 8%, against Escherichia coli . In conclusion, organic matter and surfactants compromise the antimicrobial activity of tea tree oil, although these effects vary between organisms. Clin Exp Immunol, 1999 Mar, 115(3), 491 - 7 Candida albicans suppresses nitric oxide (NO) production by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages; Chinen T et al.; We examined the in vitro effect of Candida albicans on NO production by macrophages . Candida albicans suppressed not only NO production but also expression of inducible NO synthase (iNOS) mRNA by murine IFN-gamma and bacterial LPS-stimulated peritoneal macrophages . The suppression was not associated with inhibition but rather stimulation of IL-1 beta production . This effect was observed when more than 1 x 10(3)/ml of Candida albicans were added to macrophage cultures (1 x 10(6) cells/ml) and reached a maximal level at 1 x 10(6)/ml . The NO inhibitory effect of Candida albicans was mediated predominantly by as yet unidentified soluble factor(s) and to a lesser extent by direct contact . In addition, heat- or paraformaldehyde-killed Candida albicans did not show this inhibitory activity . Culture supernatant of Candida albicans also inhibited NO production by activated macrophages in a dose-dependent manner, and increased IL-1 beta production . Finally, the inhibitory effect was not mediated by IL-10 and transforming growth factor-beta (TGF-beta), since neutralizing antibodies to these cytokines did not influence Candida albicans-induced reduction in macrophage NO production . Our results suggest that Candida albicans may evade host defence mechanism(s) through a soluble factor-mediated suppression of NO production by stimulated macrophages, and that the effect is independent of production of immunosuppressive cytokines such as IL-10 and TGF-beta. Thorax, 1998 Aug, 53 Suppl 2, S47 - 51 Role of the indoor environment in determining the severity of asthma; Woodcock A et al.; Allergen exposure can confound the management of asthma . To understand the potential mechanisms by which allergens increase the steroid requirements in atopic asthmatics, we examined the effects of allergens on glucocorticoid receptor (GCR) binding affinity and glucocorticoid (GC) responsiveness of peripheral blood mononuclear cells (PBMC) from atopic asthmatics . A significant reduction (p < 0.001) in the GCR binding affinity (Kd) was observed in ragweed-allergic asthmatics during ragweed pollen season compared with PBMC obtained before and after ragweed season . In vitro effects of allergen on PBMC GCR Kd were also examined by incubating PBMC from atopic asthmatics with allergen (ragweed and cat) versus Candida albicans . GCR binding affinity was significantly reduced after incubation with ragweed (p < 0.001) or cat allergen (p < 0.001) compared with baseline or C . albicans stimulation . This effect was limited to atopic asthmatics in that in vitro cat allergen incubation for 48 h failed to significantly alter GCR binding affinity in nonasthmatic, atopic individuals . These allergen-induced reductions in GCR binding affinity also rendered the PBMC less sensitive to the inhibitory effects of hydrocortisone and dexamethasone on allergen-induced proliferation (p < 0.01) . To test the hypothesis that allergen-induced alterations in GCR binding affinity were cytokine-induced, we examined the effects of interleukin-2 (IL-2) and IL-4 neutralization using anticytokine antibodies . Addition of both anti-IL-2 and anti-IL-4 antibodies resulted in a significant (p < 0.001) inhibition of allergen-induced alterations in GCR binding affinity . Furthermore incubation with cat allergen induced significantly higher concentrations of IL-2 (p = 0.03) and IL-4 (p = 0.02) by PBMC from atopic as compared with nonatopic subjects . Our current observations suggest that allergen exposure may contribute to poor asthma control by reducing GCR binding affinity in mononuclear cells . This appears to be mediated through IL-2 and IL-4 . These findings may have important implications for novel approaches to the treatment of poorly controlled asthma. J Clin Pathol, 1998 Nov, 51(11), 857 - 9 Immunocytochemical detection of Candida albicans in formalin fixed, paraffin embedded material; Williams DW et al.; AIM: To assess the ability of the commercially available monoclonal antibody 1B12 (BioGenex, San Ramon, USA) to identify C albicans in formalin fixed, paraffin wax embedded material (FFPE) . METHODS: Broth cultures of 20 strains of seven Candida species were resuspended in 4% agarose blocks, fixed in formalin for 24 hours, and embedded in paraffin wax . In addition, 16 blocks of FFPE tissue known to contain periodic acid-Schiff positive fungal hyphae were examined . Antigen retrieval involved microwave treatment of specimens in citrate buffer (0.01 M; pH 6.5) before addition of 1B12 antibody for 24 hours . Bound antibody was subsequently detected using a biotinylated link antibody and a peroxidase conjugated streptavidin . RESULTS: Only C albicans strains were 1B12 positive in the agarose blocks . All FFPE tissue blocks were found to contain 1B12 positive hyphal structures, indicating the presence of C albicans . CONCLUSIONS: The ability to identify candida organisms penetrating the lesional tissue in cases of chronic hyperplastic candidosis will help to clarify the role of individual Candida spp in this important form of oral candidosis. J Infect Dis, 1999 May, 179(5), 1301 - 4 Modulation of neutrophil-mediated activity against the pseudohyphal form of Candida albicans by granulocyte colony-stimulating factor (G-CSF) administered in vivo; Gaviria JM et al.; Renewed interest in neutrophil transfusions has emerged with the development and clinical use of granulocyte colony-stimulating factor (G-CSF) . G-CSF not only increases neutrophil (polymorphonuclear leukocyte, PMNL) production but also modulates various physiological properties of PMNL . The effects of G-CSF on PMNL-mediated fungicidal activity were evaluated by administration of G-CSF (300 micrograms/day subcutaneously) to 5 healthy volunteers for 6 days . G-CSF significantly enhanced PMNL-mediated damage of Candida albicans pseudohyphae by 33% (P=.007) on day 2 and by 44% (P=.04) on day 6 at a 10:1 effector:target ratio . In contrast, the ability of PMNL to induce damage of hyphae from either Fusarium solani or Aspergillus fumigatus did not significantly change during the study period . These data demonstrate that G-CSF administered in vivo modulates PMNL-mediated fungicidal activity against the pseudohyphal form of C . albicans, thereby suggesting potential utility of G-CSF as a biologic response-modifying therapy in some opportunistic fungal infections. Eur J Clin Microbiol Infect Dis, 1999 Jan, 18(1), 59 - 61 Susceptibility of Candida species isolated from female prostitutes with vulvovaginitis to antifungal agents and boric acid; Otero L et al.; The aim of this study was to determine the antifungal susceptibility of 108 Candida albicans and 23 Candida glabrata isolates obtained from female prostitutes with vulvovaginitis, a population for which available data is limited . Amphotericin B, flucytosine, and fluconazole were tested by broth microdilution, and boric acid was tested by the agar dilution method . The susceptibility patterns found in this population were the same as those in the general population . Candida glabrata required greater concentrations of boric acid for inhibition in vitro than did Candida albicans. Int J Dermatol, 1999 Feb, 38(2), 119 - 21 Cutaneous infections by papillomavirus, herpes zoster and Candida albicans as the only manifestation of idiopathic CD4+ T lymphocytopenia; Manchado Lopez P et al.; BACKGROUND: Selective depletion of CD4+ T lymphocytes is common in both primary and secondary immunodeficiencies . Idiopathic CD4+ T lymphocytopenia (ICL) cases are defined as a persistent CD4+ T lymphocyte count of less than 300x10(6) cells/L and/or less than 20% of the total T-cell count . METHOD: A 40-year-old woman, with a history of psoriasis and paracetamol allergy, presented with persistent warts of the hands and condylomas of the ano-genitalia . Histological and virological analysis was carried out on genital and cutaneous lesions and peripheral blood . RESULTS: Serology for HIV-1, HIV-2, Epstein-Barr virus and parvovirus B19 were negative . There was lymphopenia of 10% CD4+ cells, with normal numbers of total leukocytes; there were no other-abnormal immunological findings . DNA analysis of cutaneous lesions revealed HPV-49 and HPV-3 in the hands and HPV-6 in the genital region . CONCLUSIONS: The cause of the ICL in this patient is unknown . HPV is not known to be an immunosuppressive agent; it remains to be determined whether the HPV-associated lesions are the cause or the result of immunosuppression. Med Clin (Barc), 1999 Feb 20, 112(6), 211 - 4 {Epidemiology of yeast colonization and oropharyngeal infection other than Candida albicans in patients with HIV infection}; Masia Canuto MM et al.; BACKGROUND: An increasing frequency of opportunistic fungal infections in immunosuppressed patients in recent years . Concurrent with this finding, it has been noted an increasing use of fluconazole . In addition, non-Candida albicans species (NCAS), most of which are fluconazole-resistant have been increasing isolated . The aim of this study was to investigate the epidemiology of colonization and infection due to NCAS in HIV-infected patients . PATIENTS AND METHODS: A cross sectional study was conducted with HIV-infected patients in different stages, who were attended at two hospitals in Alicante, Spain . We assessed the prevalence and microbiology of oropharyngeal colonization and infection due to Candida spp., and its fluconazole susceptibility patterns . To determine the clinical risk factors for the development of fluconazole resistance, we carried out a case-control study with prevalent cases . RESULTS: We studied 168 strains from 153 patients . NCAS were isolated in 32 (21%) of them, 25 (77%) were colonized, and 5 (26%) had infection due to NCAS . The most common isolate was Candida glabrata (n = 15) . MICs were significantly higher for NCAS than for Candida albicans species, with a MIC50 of 16 and 0.25 microgram/ml, respectively, and a MIC90 of 128 micrograms/ml and 8 micrograms/ml (p = 0.0001) . The median CD4 cell count in patients with NCAS was 0.06 x 10(9)/l, and 0.19 x 10(9)/l patients with Candida albicans (p = 0.009) . Overall, 56% of the patients with NCAS and 41% of the patients with Candida albicans had been treated with fluconazole (p = 0.1) . CONCLUSIONS: NCAS are isolated in a high proportion of HIV infected patients . Most of the NCAS have a decreased susceptibility to fluconazole . The only risk factor associated with the acquisition of NCAS in HIV-infected patients is an advanced immunosuppression. Phytother Res, 1999 Mar, 13(2), 151 - 6 Antimicrobial triterpenes from Ilex integra and the mechanism of antifungal action; Haraguchi H et al.; Antimicrobial triterpenes were isolated from the fruits of Ilex integra . Their structures were elucidated by spectral data and identified as rotundic acid (1), ulsolic acid (2) and peduncloside (3) . Triterpene 1 showed significantly broad antimicrobial activity against bacteria, yeast and filamentous fungi . The antifungal activity of 1 was reversed by fatty acids . Cellular constituents leaked from Candida albicans cells incubated with triterpene 1 . These results suggest that the antimicrobial activity of triterpenes in I . integra is due to a change of membrane permeability arising from membrane lipid alteration. Hosp Pharm, 1993 Jan, 28(1), 11 - 3, 16-8 Evaluation of an aseptic technique testing and challenge kit (ATTACK); Turco S et al.; Currently, there is considerable discussion and concern about quality assurance when sterile pharmaceuticals are prepared by pharmacists and other health professionals . This study describes the utility of a kit made by Marsam Pharmaceutics Inc . in detecting microbial contamination during simulated drug transfers by syringe . Common microbial detection techniques were incorporated in a simple series of transfers intended to simulate actual use . Growth promotion studies were carried out using Trypticase Soy Broth initially in tubes and then in vials (as supplied in the kit) . Three test organisms were employed (Staphylococcus epidermidis, Bacillus subtilis, and Candida albicans) and inoculated at three levels, < 1000, < 100, and < 10 CFU/mL . All studies demonstrated growth occurring in 100% of the trials in 8 days . Similar studies were initiated in stored media (32 month) to determine the effects of time on the ability of the medium to support growth . Growth promoting ability of 32 month old media showed no significant difference . 100% of the vials inoculated showed growth in 8 days . Once the growth promoting qualities of the medium and vials was established a kit was developed then a study to determine the effectiveness of the kit as used was undertaken . Kits were manipulated according to the directions for use by a trained individual, under aseptic conditions and by an untrained individual in an area described as less than desirable . No growth occurred in the vials of the 10 kits used to illustrate good technique and good environmental conditions with 30% (3 of 10) of the kits showing contamination when transfers by syringe were carried out in the less than desirable setting.(ABSTRACT TRUNCATED AT 250 WORDS) Antimicrob Agents Chemother, 1999 Apr, 43(4), 830 - 5 LY303366 exhibits rapid and potent fungicidal activity in flow cytometric assays of yeast viability; Green LJ et al.; LY303366 is a semisynthetic analog of the antifungal lipopeptide echinocandin B that inhibits (1,3)-beta-D-glucan synthase and exhibits efficacy in animal models of human fungal infections . In this study, we utilized flow cytometric analysis of propidium iodide uptake, single-cell sorting, and standard microbiological plating methods to study the antifungal effect of LY303366 on Saccharomyces cerevisiae and Candida albicans . Our data indicate that an initial 5-min pulse treatment with LY303366 caused yeasts to take up propidium iodide and lose their ability to grow . Amphotericin B and cilofungin required longer exposure periods (30 and 180 min, respectively) and higher concentrations to elicit these fungicidal effects . These two measurements of fungicidal activity by LY303366 were highly correlated (r > 0.99) in concentration response and time course experiments . As further validation, LY303366-treated yeasts that stained with propidium iodide were unable to grow in single-cell-sorted cultures . Our data indicate that LY303366 is potent and rapidly fungicidal for actively growing yeasts . The potency and rapid action of this new fungicidal compound suggest that LY303366 may be useful for antifungal therapy. Antimicrob Agents Chemother, 1999 Apr, 43(4), 763 - 8 Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans; Ha KC et al.; Oral infections caused by the yeast Candida albicans are some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients . The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals . Several molecular mechanisms that contribute to drug resistance have been identified . In C . albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the