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Review
. 2022 Jun 17;12(6):845.
doi: 10.3390/biom12060845.

Genomic Variation-Mediating Fluconazole Resistance in Yeast

Wen-Yao Wang  1 , Hong-Qing Cai  1 , Si-Yuan Qu  1 , Wei-Hao Lin  1 , Cheng-Cheng Liang  1 , Hao Liu  1 , Ze-Xiong Xie  1 , Ying-Jin Yuan  1
Affiliations
Review

Genomic Variation-Mediating Fluconazole Resistance in Yeast

Wen-Yao Wang et al. Biomolecules. .

Abstract

Fungal infections pose a serious and growing threat to public health. These infections can be treated with antifungal drugs by killing hazardous fungi in the body. However, the resistance can develop over time when fungi are exposed to antifungal drugs by generating genomic variations, including mutation, aneuploidy, and loss of heterozygosity. The variations could reduce the binding affinity of a drug to its target or block the pathway through which drugs exert their activity. Here, we review genomic variation-mediating fluconazole resistance in the yeast Candida, with the hope of highlighting the functional consequences of genomic variations for the antifungal resistance.

Keywords: aneuploidy; antifungal resistance; fluconazole; genomic variations; loss of heterozygosity; yeast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The mechanisms of drug resistance in fungi. (A) The resistance is induced by abnormal sterol substitution or accumulation. (B) The resistance is induced by abnormal efflux pump function.
Figure 2
Figure 2
The aneuploidy-mediated fluconazole resistance. (A) The segmental aneuploidy i(5L) is related to fluconazole resistance in yeast. (B) The trisomy of chr3 is related to fluconazole resistance.
Figure 3
Figure 3
Three different types of LOH are associated with fluconazole resistance in yeast. (A) Short-range LOH that is usually produced by gene conversion through drug-resistant mutant genes, leading to an increased copy number of drug-resistant genes. (B) Long-range LOH. It results from RCO or BIR events, with intact replication or exchange from the break site to the telomere. (C) Whole-chromosome LOH. Nondisjunction or chromosome missegregation events can yield trisomic or monosomic progeny, respectively. Whole-chromosome LOH arises by either loss of the heterozygous homolog in trisomic individuals or reduplication of the hemizygous homolog in monosomic individuals. TAC1* and ERG11* represent the genes with mutations.
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References

    1. Bongomin F., Gago S., Oladele R.O., Denning D.W. Global and multi-national prevalence of fungal diseases-estimate precision. J. Fungi. 2017;3:57. doi: 10.3390/jof3040057. - DOI - PMC - PubMed
    1. Almeida F., Rodrigues M.L., Coelho C. The still underestimated problem of fungal diseases worldwide. Front. Microbiol. 2019;10:214. doi: 10.3389/fmicb.2019.00214. - DOI - PMC - PubMed
    1. Bhattacharya S., Sae-Tia S., Fries B.C. Candidiasis and mechanisms of antifungal resistance. Antibiotics. 2020;9:312. doi: 10.3390/antibiotics9060312. - DOI - PMC - PubMed
    1. Costa-de-Oliveira S., Rodrigues A.G. Candida albicans antifungal resistance and tolerance in bloodstream infections: The triad yeast-host-antifungal. Microorganisms. 2020;8:154. doi: 10.3390/microorganisms8020154. - DOI - PMC - PubMed
    1. Shapiro R.S., Robbins N., Cowen L.E. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol. Mol. Biol. Rev. 2011;75:213–267. doi: 10.1128/MMBR.00045-10. - DOI - PMC - PubMed

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