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In Vitro Activities of 2,4-Diaminoquinazoline and 2,4-Diaminopteridine Derivatives against Plasmodium falciparum. Sheila Ommeh, 2004.The activities of 28 6-substituted 2,4-diaminoquinazolines, 2,4-diamino-5,6,7,8-tetrahydroquinazolines, and 2,4-diaminopteridines against Plasmodium falciparum were tested . The 50% inhibitory concentrations (IC50s) of six compounds were <50 nM, and the most potent compound was 2,4-diamino-5-chloro-6-[N-(2,5-dimethoxybenzyl)amino]quinazoline (compound 1), with an IC50 of 9 nM . The activity of compound 1 was potentiated by the dihydropteroate synthase inhibitor dapsone, an indication that these compounds are inhibitors of dihydrofolate reductase . Further studies are warranted to assess the therapeutic potential of this combination in vivo . Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides. Andrea Giacometti, 2004.The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides was investigated in a subcutaneous rat pouch model . Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs . Differential Regulation of Multiple Proteins of Escherichia coli and Salmonella enterica Serovar Typhimurium by the Transcriptional Regulator SlyA. Andrea Spory, 2002.SlyA is a transcriptional regulator of Escherichia coli, Salmonella enterica, and other bacteria belonging to the Enterobacteriaceae . The SlyA protein has been shown to be involved in the virulence of S . enterica serovar Typhimurium, but its role in E . coli is unclear . In this study, we employed the proteome technology to analyze the SlyA regulons of enteroinvasive E . coli (EIEC) and Salmonella serovar Typhimurium . In both cases, comparative analysis of the two-dimensional protein maps of a wild-type strain, a SlyA-overproducing derivative, and a corresponding slyA mutant revealed numerous proteins whose expression appeared to be either positively or negatively controlled by SlyA . Twenty of the putative SlyA-induced proteins and 13 of the putative SlyA-repressed proteins of the tested EIEC strain were identified by mass spectrometry . The former proteins included several molecular chaperones (GroEL, GroES, DnaK, GrpE, and CbpA), proteins involved in acid resistance (HdeA, HdeB, and GadA), the "starvation lipoprotein" (Slp), cytolysin ClyA (HlyE or SheA), and several enzymes involved in metabolic pathways, whereas most of the latter proteins proved to be biosynthetic enzymes . Consistently, the resistance of the EIEC slyA mutant to heat and acid stress was impaired compared to that of the wild-type strain . Furthermore, the implication of SlyA in the regulation of several of the identified E . coli proteins was confirmed at the level of transcription with lacZ fusions . Twenty-three of the Salmonella serovar Typhimurium proteins found to be affected by SlyA were also identified by mass spectrometry . With the exception of GroEL these differed from those identified in the EIEC strain and included proteins involved in various processes . The data suggest that gene regulation by SlyA might be crucial for intracellular survival and/or replication of both EIEC and Salmonella serovar Typhimurium in phagocytic host cells . Regulation and Physiological Significance of ClpC and ClpP in Streptococcus mutans. José A. C. Lemos, 2002.Tolerance of environmental stress, especially low pH, by Streptococcus mutans is central to the virulence of this organism . The Clp ATPases are implicated in the tolerance of, and regulation of the response to, stresses by virtue of their protein reactivation and remodeling activities and their capacity to target misfolded proteins for degradation by the ClpP peptidase . The purpose of this study was to dissect the role of selected clp genes in the stress responses of S . mutans, with a particular focus on acid tolerance and adaptation . Homologues of the clpB, clpC, clpE, clpL, clpX, and clpP genes were identified in the S . mutans genome . The expression of clpC and clpP, which were chosen as the focus of this study, was induced at low pH and at growth above 40°C . Inactivation of ctsR, the first of two genes in the clpC operon, demonstrated that CtsR acts as a repressor of clp and groES-EL gene expression . Strains lacking ClpP, but not strains lacking ClpC, were impaired in their ability to grow under stress-inducing conditions, formed long chains, aggregated in culture, had reduced genetic transformation efficiencies, and had a reduced capacity to form biofilms . Comparison of two-dimensional protein gels from wild-type cells and the ctsR and clpP mutants revealed many changes in the protein expression patterns . In particular, in the clpP mutant, there was an increased production of GroESL and DnaK, suggesting that cells were stressed, probably due to the accumulation of denatured proteins . Ralstonia eutropha H16 Encodes Two and Possibly Three Intracellular Poly[D-(-)-3-Hydroxybutyrate] Depolymerase Genes. Gregory M. York, 2003.Intracellular poly[D-(-)-3-hydroxybutyrate] (PHB) depolymerases degrade PHB granules to oligomers and monomers of 3-hydroxybutyric acid . Recently an intracellular PHB depolymerase gene (phaZ1) from Ralstonia eutropha was identified . We now report identification of candidate PHB depolymerase genes from R . eutropha, namely, phaZ2 and phaZ3, and their characterization in vivo . phaZ1 was used to identify two candidate depolymerase genes in the genome of Ralstonia metallidurans . phaZ1 and these genes were then used to design degenerate primers . These primers and PCR methods on the R . eutropha genome were used to identify two new candidate depolymerase genes in R . eutropha: phaZ2 and phaZ3 . Inverse PCR methods were used to obtain the complete sequence of phaZ3, and library screening was used to obtain the complete sequence of phaZ2 . PhaZ1, PhaZ2, and PhaZ3 share  30% sequence identity . The function of PhaZ2 and PhaZ3 was examined by generating R . eutropha H16 deletion strains ( phaZ1,
phaZ2,
phaZ3,
phaZ1phaZ2,
phaZ1phaZ3,
phaZ2phaZ3, and
phaZ1phaZ2phaZ3) . These strains were analyzed for PHB production and utilization under two sets of conditions . When cells were grown in rich medium, PhaZ1 was sufficient to account for intracellular PHB degradation . When cells that had accumulated
80% (cell dry weight) PHB were subjected to PHB utilization conditions, PhaZ1 and PhaZ2 were sufficient to account for PHB degradation . PhaZ2 is thus suggested to be an intracellular depolymerase . The role of PhaZ3 remains to be established .
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