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In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus. William J. Steinbach, 2004.The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents . The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly called rapamycin) exhibit in vitro and in vivo activity against Candida albicans, Cryptococcus neoformans, and Saccharomyces cerevisiae, including fungicidal synergy with azole antifungals . We report here that both FK506 and CY exhibit a clear in vitro positive interaction with caspofungin against Aspergillus fumigatus by disk diffusion, microdilution checkerboard, and gross and microscopic morphological analyses . Microscopic morphological analyses indicate that the calcineurin inhibitors delay filamentation, and in combination with caspofungin there is a positive interaction . Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and existing antifungal agents to augment activity against A . fumigatus . Roles of the recJ and recN Genes in Homologous Recombination and DNA Repair Pathways of Neisseria gonorrhoeae. Eric P. Skaar, 2002.The paradigm of homologous recombination comes from Escherichia coli, where the genes involved have been segregated into pathways . In the human pathogen Neisseria gonorrhoeae (the gonococcus), the pathways of homologous recombination are being delineated . To investigate the roles of the gonococcal recN and recJ genes in the recombination-based processes of the gonococcus, these genes were inactivated in the N . gonorrhoeae strain FA1090 . We report that both recN and recJ loss-of-function mutants show decreased DNA repair ability . In addition, the recJ mutant was decreased in pilus-dependent colony morphology variation frequency but not DNA transformation efficiency, while the recN mutant was decreased in DNA transformation efficiency but not pilus-dependent variation frequency . We were able to complement all of these deficiencies by supplying an ectopic functional copy of either recJ or recN at an irrelevant locus . These results describe the role of recJ and recN in the recombination-dependent processes of the gonococcus and further define the pathways of homologous recombination in this organism . Identification and Characterization of the gerH Operon of Bacillus anthracis Endospores: a Differential Role for Purine Nucleosides in Germination. Matthew A. Weiner, 2003.We identified a tri-cistronic operon, gerH, in Bacillus anthracis that is important for endospore germination triggered by two distinct germination response pathways termed inosine-His and purine-Ala . Together, the two pathways allow B . anthracis endospores a broader recognition of purines and amino acids that may be important for host-mediated germination . Dibenzyl Sulfide Metabolism by White Rot Fungi. Jonathan D. Van Hamme, 2003.Microbial metabolism of organosulfur compounds is of interest in the petroleum industry for in-field viscosity reduction and desulfurization . Here, dibenzyl sulfide (DBS) metabolism in white rot fungi was studied . Trametes trogii UAMH 8156, Trametes hirsuta UAMH 8165, Phanerochaete chrysosporium ATCC 24725, Trametes versicolor IFO 30340 (formerly Coriolus sp.), and Tyromyces palustris IFO 30339 all oxidized DBS to dibenzyl sulfoxide prior to oxidation to dibenzyl sulfone . The cytochrome P-450 inhibitor 1-aminobenzotriazole eliminated dibenzyl sulfoxide oxidation . Laccase activity (0.15 U/ml) was detected in the Trametes cultures, and concentrated culture supernatant and pure laccase catalyzed DBS oxidation to dibenzyl sulfoxide more efficiently in the presence of 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) than in its absence . These data suggest that the first oxidation step is catalyzed by extracellular enzymes but that subsequent metabolism is cytochrome P-450 mediated .
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