title: Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species.
abstract: Work in Saccharomyces cerevisiae and Cryptococcus neoformans suggests that caspofungin could interact with the calcineurin pathway. We examined the in vitro interaction of caspofungin with calcineurin inhibitors (FK506, cyclosporin, FK520 and L685,818) and the TOR inhibitor rapamycin in 13 isolates of Aspergillus species. Caspofungin activity was enhanced by calcineurin/TOR inhibitors for all Aspergillus isolates studied. Further investigation of this pathway is warranted.
authors.affiliation: Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 402, Houston, TX 77030, USA. dkontoyi@mdanderson.org
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Albert
authors.forename: Gregory S
authors.initials: GS
authors.lastname: May
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development*; D065095:Calcineurin Inhibitors; D000077336:Caspofungin; D004338:Drug Combinations; D054714:Echinocandins; D005964:Glucosyltransferases / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D055666:Lipopeptides; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D004338:Drug Combinations; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D008565:Membrane Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D029701:Saccharomyces cerevisiae Proteins; C076383:L 685818; C058028:immunomycin; D005964:Glucosyltransferases; C091618:FKS1 protein, S cerevisiae; C095724:GSC2 protein, S cerevisiae; D000077336:Caspofungin; D020123:Sirolimus; D016559:Tacrolimus