In:
Mycoses, Wiley, Vol. 61, No. 7 ( 2018-07), p. 430-440
Abstract:
Recently, Candida glabrata has emerged as a health‐threatening pathogen and the rising resistance to antifungal agent in C. glabrata often leads to clinical treatment failure. To investigate the evolution of drug resistance and adherence ability in four paired clinical isolates collected before and after antifungal treatment. Sequence analysis, gene disruption, drug‐susceptibility, adhesion tests and real‐time quantitative PCR were performed. The azole‐susceptible strains acquired azole resistance after antifungal therapy. Four gain‐of‐function ( GOF ) mutations in Cg PDR 1 were revealed by sequence analysis, namely G1099D, G346D, L344S and P927S, the last being reported for the first time. CDR 1 , CDR 2 and SNQ 2 efflux pump gene expression levels were elevated in strains harbouring GOF mutations in Cg PDR 1 , resulting in decreased azole susceptibility. Cg PDR 1 alleles with distinct GOF mutations displayed different expression profiles for the drug‐related genes. Cg PDR 1 GOF mutations led to increased efflux pumps expression levels in a strain background independent way. Hyperactive Pdr1 G1099D and Pdr1 P927S displayed strain background‐dependent increased adherence to host cells via upregulation of EPA 1 transcription. Interestingly, the drug transporter gene expression levels did not always correspond with that of the adhesin EPA 1 gene. GOF mutations in Cg PDR 1 conferred drug resistance and increased adherence in the clinical strains, possibly endowing C. glabrata with increased viability and pathogenicity.
Type of Medium:
Online Resource
ISSN:
0933-7407
,
1439-0507
DOI:
10.1111/myc.2018.61.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020780-3
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