Constitutive activation of the PDR16 promoter in a Candida albicans azole-resistant clinical isolate overexpressing CDR1 and CDR2.
نویسندگان
چکیده
Candida albicans azole-resistant clinical isolates overexpressing the CDR1 and CDR2 genes (multidrug transporters) also overexpress the PDR16 gene (phosphatidylinositol transfer protein). We show here that the PDR16 promoter displays higher transcriptional activity following integration in an azole-resistant isolate than in the matched azole-susceptible one. Thus, the upregulation of PDR16 in the resistant strain results from a mutation acting in trans.
منابع مشابه
Relative contributions of the Candida albicans ABC transporters Cdr1p and Cdr2p to clinical azole resistance.
Candida albicans frequently develops resistance to treatment with azole drugs due to the acquisition of gain-of-function mutations in the transcription factor Tac1p. Tac1p hyperactivation in azole-resistant isolates results in the constitutive overexpression of several genes, including CDR1 and CDR2, which encode two homologous transporters of the ATP-binding cassette family. Functional studies...
متن کاملProteomic analysis of Mrr1p- and Tac1p-associated differential protein expression in azole-resistant clinical isolates of Candida albicans.
Azole resistance in Candida albicans is frequently caused by the overexpression of multi-drug efflux pump genes MDR1, CDR1, and CDR2 due to gain-of-function mutations in the zinc cluster transcription factors Mrr1p and Tac1p. In this study, we performed a comparative proteomic analysis to identify proteins whose expression level is influenced by these transcription factors. Both 2-DE and PMF we...
متن کاملCloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene.
Resistance to azole antifungal agents in Candida albicans can be mediated by multidrug efflux transporters. In a previous study, we identified at least two such transporters, Cdr1p and Benp, which belong to the class of ATP-binding cassette (ABC) transporters and of major facilitators, respectively. To isolate additional factors potentially responsible for resistance to azole antifungal agents ...
متن کاملUsing PCR to Compare the Expression of CDR1, CDR2, and MDR1 in Candida Albicans Isolates Resistant and Susceptible to Fluconazole
Abstract Background and objectives: More Candida albicans strains are reported resistant to fluconazole in patients with AIDS, cancer and organ recipients. Fluconazole resistance can be attributed to changes in pathways of sterol biosynthesis, mutation in or overexpression of ERG11 and the expression of CDR1, CDR2, and MDR1. This study aimed to compare the ex...
متن کاملGenome-wide expression and location analyses of the Candida albicans Tac1p regulon.
A major mechanism of azole resistance in Candida albicans is overexpression of the genes encoding the ATP binding cassette transporters Cdr1p and Cdr2p due to gain-of-function mutations in Tac1p, a transcription factor of the zinc cluster family. To identify the Tac1p regulon, we analyzed four matched sets of clinical isolates representing the development of CDR1- and CDR2-mediated azole resist...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 48 7 شماره
صفحات -
تاریخ انتشار 2004