Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azoles.
Candida parapsilosis is a common isolate from clinical fungal infectious episodes. Resistance of C. parapsilosis to azoles has been increasingly reported. To analyse the development of resistance in C. parapsilosis, four azole-susceptible clinical strains and one American Type Culture Collection type strain were cultured in the presence of fluconazole, voriconazole and posaconazole at different concentrations. The isolates developed variable degrees of azole resistance according to the antifungal used. Fluconazole was the fastest inducer while posaconazole was the slowest. Fluconazole and voriconazole induced resistance to themselves and each other, but not to posaconazole. Posaconazole induced resistance to all azoles. Developed resistance was stable; it could be confirmed after 30 days of subculture in drug-free medium. Azole-resistant isolates revealed a homogeneous population structure; the role of azole transporter efflux pumps was minor after evaluation by microdilution and cytometric assays with efflux pump blockers (verapamil, ibuprofen and carbonyl cyanide 3-chloro-phenylhydrazone). We conclude that the rapid development of azole resistance occurs by a mechanism that might involve mutation of genes responsible for ergosterol biosynthesis pathway, stressed by exposure to antifungals.
Pinto e Silva
Ana Teresa
AT
Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal. anatpsilva@hotmail.com
Costa-de-Oliveira
Sofia
S
Silva-Dias
Ana
A
Pina-Vaz
Cidália
C
Rodrigues
Acácio Gonçalves
AG
D000935:Antifungal Agents / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000235:genetics; D002175:Candida / Q000187:drug effects*; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000096:biosynthesis; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole; D065819:Voriconazole; D004875:Ergosterol