title: Fungicidal activity and morphological alterations of Candida albicans induced by echinocandins: study of strains with reduced caspofungin susceptibility.
abstract: Caspofungin is a member of the echinocandin class of antifungal compounds that inhibit 1,3-β-d-Glucan synthase. As patient exposure to caspofungin (CAS) broadens, the number of infecting strains with reduced susceptibility to this drug is expected to rise. In the present study, the in vitro effects of varying concentrations of CAS against Candida albicans isolates presenting reduced susceptibility to CAS were studied in comparison with a reference strain. Two C. albicans isolates presenting high minimal inhibitory concentrations (MIC = 8 μg ml(-1) ) were selected: one isolate obtained in the laboratory under continuous antifungal selection pressure (CaIn-R) and one clinical isolate (CaClin-R) from a patient with a therapeutic failure. Results showed that after 24 h of CAS exposure, CaIn-R and CaClin-R presented a partial growth inhibition in comparison with the reference strain. Moreover, scanning electron microscopy and transmission electron microscopy studies showed that the cell walls of CaIn-R and CaClin-R were less altered than that of the reference strain. These observations suggested that although CaIn-R and CaClin-R cells were misshapen after CAS exposure, cell lysis was limited after 24 h of treatment indicating higher survival ability for CaIn-R and CaClin-R in the presence of CAS.
authors.affiliation: Laboratoire de Parasitologie et Mycologie Médicale, UMR 145 IRD/Université Montpellier I VIH/SIDA et Maladies Associées, Faculté de Pharmacie, Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dunyach
authors.forename: Pascal
authors.initials: P
authors.lastname: Drakulovski
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bertout
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jouvert
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Michèle
authors.initials: M
authors.lastname: Mallié
mesh_terms: D000935:Antifungal Agents / Q000633:toxicity*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000633:toxicity*; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin