Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States

ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for...

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Autores principales:	Amanda C. Smith, Meleah A. Hickman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans fitness genome stability host-pathogen interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3409c403985d4e2bb9f246e8a263d11b
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spelling	oai:doaj.org-article:3409c403985d4e2bb9f246e8a263d11b2021-11-15T15:30:15ZHost-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States10.1128/mSphere.00433-202379-5042https://doaj.org/article/3409c403985d4e2bb9f246e8a263d11b2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00433-20https://doaj.org/toc/2379-5042ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated C. albicans predominantly decreased host reproductive fitness, whereas tetraploid host-associated C. albicans increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter its relationship with the host. IMPORTANCE Candida albicans is an opportunistic fungal pathogen of humans. The ability to generate genetic variation is essential for adaptation and is a strategy that C. albicans and other fungal pathogens use to change their genome size. Stressful environments, including the host, induce C. albicans genome instability. Here, we investigated how C. albicans genetic background and ploidy state impact genome instability, both in vitro and in a host environment. We show that the host environment induces genome instability, but the magnitude depends on C. albicans genetic background. Furthermore, we show that tetraploid C. albicans is highly unstable in host environments and rapidly reduces in genome size. These reductions in genome size often resulted in reduced virulence. In contrast, diploid C. albicans displayed modest host-induced genome size changes, yet these frequently resulted in increased virulence. Such studies are essential for understanding how opportunistic pathogens respond and potentially adapt to the host environment.Amanda C. SmithMeleah A. HickmanAmerican Society for MicrobiologyarticleCandida albicansfitnessgenome stabilityhost-pathogen interactionsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans fitness genome stability host-pathogen interactions Microbiology QR1-502
spellingShingle	Candida albicans fitness genome stability host-pathogen interactions Microbiology QR1-502 Amanda C. Smith Meleah A. Hickman Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
description	ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated C. albicans predominantly decreased host reproductive fitness, whereas tetraploid host-associated C. albicans increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter its relationship with the host. IMPORTANCE Candida albicans is an opportunistic fungal pathogen of humans. The ability to generate genetic variation is essential for adaptation and is a strategy that C. albicans and other fungal pathogens use to change their genome size. Stressful environments, including the host, induce C. albicans genome instability. Here, we investigated how C. albicans genetic background and ploidy state impact genome instability, both in vitro and in a host environment. We show that the host environment induces genome instability, but the magnitude depends on C. albicans genetic background. Furthermore, we show that tetraploid C. albicans is highly unstable in host environments and rapidly reduces in genome size. These reductions in genome size often resulted in reduced virulence. In contrast, diploid C. albicans displayed modest host-induced genome size changes, yet these frequently resulted in increased virulence. Such studies are essential for understanding how opportunistic pathogens respond and potentially adapt to the host environment.
format	article
author	Amanda C. Smith Meleah A. Hickman
author_facet	Amanda C. Smith Meleah A. Hickman
author_sort	Amanda C. Smith
title	Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
title_short	Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
title_full	Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
title_fullStr	Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
title_full_unstemmed	Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States
title_sort	host-induced genome instability rapidly generates phenotypic variation across <named-content content-type="genus-species">candida albicans</named-content> strains and ploidy states
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/3409c403985d4e2bb9f246e8a263d11b
work_keys_str_mv	AT amandacsmith hostinducedgenomeinstabilityrapidlygeneratesphenotypicvariationacrossnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentstrainsandploidystates AT meleahahickman hostinducedgenomeinstabilityrapidlygeneratesphenotypicvariationacrossnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentstrainsandploidystates
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Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across <named-content content-type="genus-species">Candida albicans</named-content> Strains and Ploidy States

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