Overexpression of CDR1 and CDR2 Genes Plays an Important Role in Fluconazole Resistance in Candida albicans with G487T and T916C Mutations

Abstract

This study was designed to investigate potential resistance mechanisms by studying the expression of resistant genes in 14 fluconazole-resistant Candida albicans isolates, with G487T and T916C mutations in the 14alpha-demethylase (ERG11) gene, collected from human immunodeficiency virus uninfected patients and a fluconazole-susceptible control strain. The in vitro susceptibilities of the C. albicans isolates to fluconazole were determined using the broth microdilution method and a disc diffusion assay. Expression of Candida drug resistance (CDR)1, CDR2, ERG11, fluconazole resistance (FLU)1 and multidrug resistance (MDR)1 genes was measured using real-time reverse transcription-polymerase chain reaction and evaluated relative to the expression of the control gene 18SrRNA. The CDR1 and CDR2 genes were upregulated in all the fluconazole-resistant C. albicans isolates, whereas only a few isolates showed high expression of MDR1, FLU1 and ERG11 genes compared with the control strain. In conclusion, overexpression of the CDR1 and CDR2 genes may play an important role in fluconazole-resistant C. albicans with G487T and T916C mutations.

Investigation of the Expression Levels of Efflux Pumps in Fluconazole-Resistant Candida albicans Isolates

“…Yapılan bir çalışmada, HIV ile enfekte hastalardan soyutlanmış FLU-R C.albicans izolatlarının ATCC 10231 kontrol suşuna göre 1.6-8 kat CDR1 ve 3.7-52 kat CDR2 geni fazla ekspresyonu yaptığı bildirilmiştir 20 . Çalışmamızda FLU-R izolatların ATCC 14053 kontrol suşuna kıyasla 1.6-32 kat CDR1, 2.6-47.2 kat CDR2 fazla ekspresyonu saptanmış ve suşları-mızın CDR1 ve CDR2 gen ekspresyon düzeylerinin paralel olduğu gözlenmiştir.…”

“…Çalışmamızda FLU-R izolatların ATCC 14053 kontrol suşuna kıyasla 1.6-32 kat CDR1, 2.6-47.2 kat CDR2 fazla ekspresyonu saptanmış ve suşları-mızın CDR1 ve CDR2 gen ekspresyon düzeylerinin paralel olduğu gözlenmiştir. Bu gözlem Chen ve arkadaşlarının 20 çalışmasında da rapor edilmiş olup, bu iki genin birlikte düzen-lendiğini göstermektedir. Araştırmamızda yapılan istatistiksel analiz sonucunda CDR1, CDR2 ve MDR1 ekspresyonları açısından FLU-R, S-KİE ve FLU-S C.albicans suşları arasında anlamlı bir fark saptanmamış olup, bu sonucun gruplarımızdaki suş sayısının az olmasın-dan kaynaklandığı düşünülmüştür.…”

Association of ADH1 and DDR48 expression with azole resistance in Candida albicans

“…Both MDR1 and FLU1 genes were over-expressed specifically in fluconazole-resistant C. albicans isolates. Disruption of FLU1 gene in C. albicans mutants with deletions in multidrug efflux transporter genes, including CDR1, CDR2 and MDR1, resulted in enhanced susceptibility to several azole derivatives, indicating the contribution of FLU1 in azole resistance [19].…”

“…in C. albicans entails the Cdr1p and Cdr2p efflux pump proteins, the functionality of which depends on energy metabolism [19,21].…”

The Etest Performed Directly on Blood Culture Bottles Is a Reliable Tool for Detection of Fluconazole-Resistant Candida albicans Isolates

“…The mechanisms responsible for azole resistance in C. albicans involve mutations in the ERG11 and ERG3 genes, overexpression of ERG11, overexpression of genes encoding efflux pumps, or a combination of the three (14,15). Fluconazole-resistant C. albicans isolates can be detected in the clinical microbiology laboratory using gold standard broth microdilution methods (CLSI and EUCAST), commercially available broth microdilution microtiter systems (Sensititre YeastOne), and agar-based methods (Etest) (16,17).…”