Evaluation of fluconazole resistance mechanisms in candida albicans clinical isolates from HIV-infected patients in Brazil.
In this study, we describe resistance mechanisms in fluconazole-resistant isolates of C. albicans isolated from AIDS patients from nine Brazilian hospitals. These mechanisms include the presence of point mutations in the ERG11 gene and overexpression of ERG11, and several genes encoding efflux pumps, as measured by quantitative real-time reverse transcriptase polymerase chain reaction. Several fluconazole-resistant strains had multiple mechanisms of resistance. Four mutations previously described, Y132F, K143R, E266D, and V437I, were identified among the strains, whereas some isolates contained more than one mutation. Fourteen novel mutations were identified. Interestingly, all Brazilian fluconazole-resistant isolates showed homozygosity at mating-type loci (MTL) associated with fluconazole resistance. This is the first comprehensive assessment at molecular level of mechanisms of fluconazole resistance in C. albicans isolates from South America.
Goldman
Gustavo H
GH
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil. ggoldman@usp.br
da Silva Ferreira
Márcia Eliana
ME
dos Reis Marques
Everaldo
E
Savoldi
Marcela
M
Perlin
David
D
Park
Steven
S
Godoy Martinez
Patricio Christian
PC
Goldman
Maria Helena S
MH
Colombo
Arnaldo L
AL
D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis* / Q000188:drug therapy; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D001938:Brazil; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics*; D002177:Candidiasis / Q000175:diagnosis* / Q000188:drug therapy; D015331:Cohort Studies; D004271:DNA, Fungal / Q000032:analysis; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D019450:Genes, MDR; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D010597:Pharmacogenetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D000935:Antifungal Agents; D004271:DNA, Fungal; D015725:Fluconazole