Fcr1p inhibits development of fluconazole resistance in Candida albicans by abolishing CDR1 induction.
Overexpression of Candida drug resistance 1 (CDR1) gene in Candida albicans (C. albicans), an efflux pump, is one of the major mechanisms contributing to drug resistance. C. albicans for fluconazole resistance 1 protein (Fcr1p) is a member of the family of zinc cluster proteins homologous to Pdr1p and Pdr3p (pleiotropic drug resistance protein) mediating azole resistance in Saccharomyces cerevisiae (S. cerevisiae) by regulating the expression of pleiotropic drug resistance 5 (PDR5) homologous to C. albicans CDR1. A previous study has showed that for fluconazole resistance 1 (FCR1) could also confer azole resistance in S. cerevisiae pdr1 pdr3 mutant by regulating PDR5. Therefore, we investigated the role of FCR1 in the development of C. albicans azole resistance in vitro and in vivo. Our results showed that Fcr1p inhibited fluconazole (FLC) resistance development in C. albicans through abolishing the induction of CDR1 expression by FLC, and in contrast FLC resistance development was accelerated resulting from the deletion of FCR1.
Shen
Hui
H
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, PR China.
An
Mao-Mao
MM
Wang
De Jun
de J
Xu
Zheng
Z
Zhang
Jun-Dong
JD
Gao
Ping-Hui
PH
Cao
Ying-Ying
YY
Cao
Yong-Bing
YB
Jiang
Yuan-Ying
YY
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use; D005456:Fluorescent Dyes / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D013997:Time Factors
D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005456:Fluorescent Dyes; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D008667:Metalloproteins; D012333:RNA, Messenger; D012235:Rhodamines; C026188:rhodamine 6G; D015725:Fluconazole