2013
DOI: 10.1128/iai.00074-13
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Gain-of-Function Mutations in PDR1 , a Regulator of Antifungal Drug Resistance in Candida glabrata, Control Adherence to Host Cells

Abstract: bCandida glabrata is an emerging opportunistic pathogen that is known to develop resistance to azole drugs due to increased drug efflux. The mechanism consists of CgPDR1-mediated upregulation of ATP-binding cassette transporters. A range of gainof-function (GOF) mutations in CgPDR1 have been found to lead not only to azole resistance but also to enhanced virulence. This implicates CgPDR1 in the regulation of the interaction of C. glabrata with the host. To identify specific CgPDR1-regulated steps of the host-p… Show more

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Cited by 61 publications
(70 citation statements)
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“…This is in contrast to what has been reported for C. glabrata, where GOF mutations in Pdr1 cause not only azole resistance but also increased virulence (39)(40)(41)(42). Considering that the fluconazole-resistant C. albicans isolates displayed reduced fitness under at least some conditions but never showed increased fitness compared to that of the matched susceptible isolates under any of the tested conditions, it is likely that, …”
Section: Fitness Of Fluconazole-resistant C Albicanscontrasting
confidence: 53%
“…This is in contrast to what has been reported for C. glabrata, where GOF mutations in Pdr1 cause not only azole resistance but also increased virulence (39)(40)(41)(42). Considering that the fluconazole-resistant C. albicans isolates displayed reduced fitness under at least some conditions but never showed increased fitness compared to that of the matched susceptible isolates under any of the tested conditions, it is likely that, …”
Section: Fitness Of Fluconazole-resistant C Albicanscontrasting
confidence: 53%
“…As a model of the interaction of yeast cells with the innate immune system, we designed a coculture phagocytosis assay with primary BMDMs (extracted from the bone marrow of mice) to ask whether the UPC2-3 allele had an influence on phagocytosis by BMDMs. We used a competitive phagocytosis assay with strains SC5314 and ALY31 labeled with GFP and RFP, respectively, as published by Vale-Silva et al (53). For this experiment, preconfluent BMDMs on cover slides were cocultured with SC5314 and ALY31 mixed in equal amounts at an MOI of 1 for 0.5 h. The percentage of internalization ratio (PIR) is displayed in Fig.…”
Section: Phenotypic Verifications Of Engineered Strainsmentioning
confidence: 99%
“…Extensive characterization in C. albicans and C. glabrata has shown that gain-of-function mutations in transcription factors, like MRR1, TAC1, UPC2, or PDR1, are involved in the develop-ment of azole resistance in these species (12)(13)(14)(15)(16)(17)(18)(19). These mutations activate the transcription factors, which constitutively upregulate their targets: efflux pumps or ergosterol biosynthesis enzymes.…”
mentioning
confidence: 99%