Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a h...

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Autores principales:	A. Forche, D. Abbey, T. Pisithkul, M. A. Weinzierl, T. Ringstrom, D. Bruck, K. Petersen, J. Berman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/00e8725c8bb24980a1fd774e1d31de09
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spelling	oai:doaj.org-article:00e8725c8bb24980a1fd774e1d31de092021-11-15T15:38:45ZStress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mBio.00129-112150-7511https://doaj.org/article/00e8725c8bb24980a1fd774e1d31de092011-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00129-11https://doaj.org/toc/2150-7511ABSTRACT Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination in C. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated during in vitro exposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus, C. albicans generates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term “stress-induced LOH” that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation. IMPORTANCE Stress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms. Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this “stress-induced LOH” facilitates the rapid adaptation of C. albicans, which does not undergo meiosis, to changing environments within the host.A. ForcheD. AbbeyT. PisithkulM. A. WeinzierlT. RingstromD. BruckK. PetersenJ. BermanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 4 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 A. Forche D. Abbey T. Pisithkul M. A. Weinzierl T. Ringstrom D. Bruck K. Petersen J. Berman Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination in C. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated during in vitro exposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus, C. albicans generates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term “stress-induced LOH” that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation. IMPORTANCE Stress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms. Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this “stress-induced LOH” facilitates the rapid adaptation of C. albicans, which does not undergo meiosis, to changing environments within the host.
format	article
author	A. Forche D. Abbey T. Pisithkul M. A. Weinzierl T. Ringstrom D. Bruck K. Petersen J. Berman
author_facet	A. Forche D. Abbey T. Pisithkul M. A. Weinzierl T. Ringstrom D. Bruck K. Petersen J. Berman
author_sort	A. Forche
title	Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
title_short	Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
title_full	Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	stress alters rates and types of loss of heterozygosity in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/00e8725c8bb24980a1fd774e1d31de09
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Stress Alters Rates and Types of Loss of Heterozygosity in <named-content content-type="genus-species">Candida albicans</named-content>

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