Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis

Yang, Feng; Lu, Hui; Wu, Hao; Fang, Ting; Berman, Judith; Jiang, Yuanying

doi:10.1128/spectrum.00508-21

Cited by 19 publications

(15 citation statements)

References 54 publications

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“…When the growing cells are re-tested, again only some progeny cells grow, implying that tolerance is a physiological or epigenetic phenomenon or that it is transient. Aneuploidy can confer resistance or tolerance as well as cross-tolerance and appears in response to a range of drugs and pathogenic yeast species [28][29][30][31][32][33] and, like copy number variation, is maintained primarily under drug pressure. Among the specific genes that affect tolerance are genes encoding transcription factors Czf1 (ref.…”

Section: Mechanisms Of Antifungal Resistance and Tolerancementioning

confidence: 99%

The importance of antimicrobial resistance in medical mycology

et al. 2022

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Prior to the SARS-CoV-2 pandemic, antibiotic resistance was listed as the major global health care priority. Some analyses, including the O’Neill report, have predicted that deaths due to drug-resistant bacterial infections may eclipse the total number of cancer deaths by 2050. Although fungal infections remain in the shadow of public awareness, total attributable annual deaths are similar to, or exceeds, global mortalities due to malaria, tuberculosis or HIV. The impact of fungal infections has been exacerbated by the steady rise of antifungal drug resistant strains and species which reflects the widespread use of antifungals for prophylaxis and therapy, and in the case of azole resistance in Aspergillus, has been linked to the widespread agricultural use of antifungals. This review, based on a workshop hosted by the Medical Research Council and the University of Exeter, illuminates the problem of antifungal resistance and suggests how this growing threat might be mitigated.

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Section: Mechanisms Of Antifungal Resistance and Tolerancementioning

confidence: 99%

The importance of antimicrobial resistance in medical mycology

et al. 2022

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“…S1 ), suggesting that, like in C. albicans , transformation is a mutagenic process in C. parapsilosis . Aneuploidies can result in dramatic phenotypic effects ( 19 – 22 ); for example, an extra copy of chromosome 6 in C. parapsilosis drives cross-tolerance to both tunicamycin and aureobasidin A ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 Editing Induces Loss of Heterozygosity in the Pathogenic Yeast Candida parapsilosis

Lombardi

Bergin

Ryan

et al. 2022

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“…These genomic changes sometimes result in phenotypic changes, such to nitrogen utilization (23), tolerance to DNA-damaging agents (24), and virulence in vivo (19). An extra copy of chromosome 6 in C. parapsilosis drives cross-tolerance to both tunicamycin and aureobasidin A (41), suggesting that aneuploidy mediates phenotypic changes in this species as well.…”

Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 editing induces Loss of Heterozygosity in the pathogenic yeast Candida parapsilosis

Lombardi

Bergin

Ryan

et al. 2022

Preprint

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Genetic manipulation is often used to study gene function. However, unplanned genome changes (including Single Nucleotide Polymorphisms (SNPs), aneuploidy and Loss of Heterozygosity (LOH)) can affect the phenotypic traits of the engineered strains. Here, we show that CRISPR-Cas9 editing can induce LOH in the diploid human pathogenic yeast Candida parapsilosis. We sequenced the genomes of ten isolates that were edited with CRISPR-Cas9 and found that the designed changes were present in nine. However, we also observed LOH in all isolates, and aneuploidy in two isolates. LOH occurred most commonly downstream of the Cas9 cut site and extended to the telomere in three isolates. In two isolates we observed LOH on chromosomes that were not targeted by CRISPR-Cas9. Two different isolates exhibited cysteine and methionine auxotrophy caused by LOH at a heterozygous site in MET10, approximately 11 and 157 kb downstream from the Cas9 target site, respectively. C. parapsilosis isolates have relatively low levels of heterozygosity. However, our results show that mutation complementation to confirm observed phenotypes is important even when using CRISPR-Cas9, which is now the gold standard of genetic engineering.

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Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis

Abstract: Candida parapsilosis is an emerging major human fungal pathogen, especially in neonates. Aneuploidy, having uneven numbers of chromosomes, is a well-known mechanism for adapting to stress in Candida albicans , the most common human fungal pathogen.

Cited by 19 publications

References 54 publications

The importance of antimicrobial resistance in medical mycology

The importance of antimicrobial resistance in medical mycology

CRISPR-Cas9 Editing Induces Loss of Heterozygosity in the Pathogenic Yeast Candida parapsilosis

CRISPR-Cas9 editing induces Loss of Heterozygosity in the pathogenic yeast Candida parapsilosis

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