Dataset Information

The Risk Factors and Mechanisms of Azole Resistance of Candida tropicalis Blood Isolates in Thailand: A Retrospective Cohort Study.

ABSTRACT: In recent decades, an epidemiological shift has been observed from Candida infections to non-albicans species and resistance to azoles. We investigated the associated factors and molecular mechanisms of azole-resistant blood isolates of C. tropicalis. Full-length sequencing of the ERG11 gene and quantitative real-time RT-PCR for the ERG11, MDR1, and CDR1 genes were performed. Male sex (odds ratio, 0.38), leukemia (odds ratio 3.15), and recent administration of azole (odds ratio 10.56) were associated with isolates resistant to azole. ERG11 mutations were found in 83% of resistant isolates, with A395T as the most common mutation (53%). There were no statistically significant differences in the expression of the ERG11, MDR1, and CDR1 genes between the groups resistant and susceptible to azole. The prevalence of azole-resistant isolates was higher than the usage of antifungal drugs, suggesting the possibility of environmental transmission in the healthcare setting. The unknown mechanism of the other 17% of the resistant isolates remains to be further investigated.

SUBMITTER: Leepattarakit T

PROVIDER: S-EPMC9604623 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Risk Factors and Mechanisms of Azole Resistance of Candida tropicalis Blood Isolates in Thailand: A Retrospective Cohort Study.

Leepattarakit Teera T Tulyaprawat Orawan O Ngamskulrungroj Popchai P

Journal of fungi (Basel, Switzerland) 20220920 10

In recent decades, an epidemiological shift has been observed from Candida infections to non-albicans species and resistance to azoles. We investigated the associated factors and molecular mechanisms of azole-resistant blood isolates of C. tropicalis. Full-length sequencing of the ERG11 gene and quantitative real-time RT-PCR for the ERG11, MDR1, and CDR1 genes were performed. Male sex (odds ratio, 0.38), leukemia (odds ratio 3.15), and recent admi ...[more]

PMID: 36294548

Similar Datasets

Project description:TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be hyperactive by a gain-of-function (GOF) point mutation responsible for constitutive high expression of CDR1/2. High azole resistance levels are achieved when C. albicans carries hyperactive alleles only as a consequence of loss of heterozygosity (LOH) at the TAC1 locus on chromosome 5 (Chr 5), which is linked to the mating-type-like (MTL) locus. Both are located on the Chr 5 left arm along with ERG11 (target of azoles). In this work, five groups of related isolates containing azole-susceptible and -resistant strains were analyzed for the TAC1 and ERG11 alleles and for Chr 5 alterations. While recovered ERG11 alleles contained known mutations, 17 new TAC1 alleles were isolated, including 7 hyperactive alleles with five separate new GOF mutations. Single-nucleotide-polymorphism analysis of Chr 5 revealed that azole-resistant strains acquired TAC1 hyperactive alleles and, in most cases, ERG11 mutant alleles by LOH events not systematically including the MTL locus. TAC1 LOH resulted from mitotic recombination of the left arm of Chr 5, gene conversion within the TAC1 locus, or the loss and reduplication of the entire Chr 5. In one case, two independent TAC1 hyperactive alleles were acquired. Comparative genome hybridization and karyotype analysis revealed the presence of isochromosome 5L [i(5L)] in two azole-resistant strains. i(5L) leads to increased copy numbers of azole resistance genes present on the left arm of Chr 5, among them TAC1 and ERG11. Our work shows that azole resistance was due not only to the presence of specific mutations in azole resistance genes (at least ERG11 and TAC1) but also to their increase in copy number by LOH and to the addition of extra Chr 5 copies. With the combination of these different modifications, sophisticated genotypes were obtained. The development of azole resistance in C. albicans is therefore a powerful instrument for generating genetic diversity.

Dataset Information

The Risk Factors and Mechanisms of Azole Resistance of Candida tropicalis Blood Isolates in Thailand: A Retrospective Cohort Study.

Publications

The Risk Factors and Mechanisms of Azole Resistance of <i>Candida tropicalis</i> Blood Isolates in Thailand: A Retrospective Cohort Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets