The Impact of Gene Dosage and Heterozygosity on the Diploid Pathobiont Candida albicans

Liang, Shen-Huan; Bennett, Richard J.

doi:10.3390/jof6010010

Cited by 26 publications

(19 citation statements)

References 134 publications

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“…Tetraploid genome reduction generates massive karyotypic heterogeneity in cell populations through its parasexual cycle (22,23) by reassorting chromosomes into new allelic combinations, which has been proposed to facilitate rapid adaptation (15). Others have demonstrated that decreased heterozygosity correlates with decreased in pathogen fitness and virulence (29,39,51). In our study, we measured genome size changes but have not yet characterized the allelic composition in our host-derived isolates.…”

Section: Discussionmentioning

confidence: 99%

Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across Candida albicans Strains and Ploidy States

Smith

Hickman

2020

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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.

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Section: Discussionmentioning

confidence: 99%

Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across Candida albicans Strains and Ploidy States

Smith

Hickman

2020

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“… 2014 ; Tso et al . 2018 ; Liang and Bennett 2019 ) as well as resistance to antifungal therapy (Coste et al . 2006 ; Ford et al .…”

Section: The Fungusmentioning

confidence: 99%

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

d’Enfert

Kaune

Alaban

et al. 2020

FEMS Microbiology Reviews

213

134

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Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

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“…A parasexual cycle commonly leads to aneuploid forms, when the yeast cells acquire an extra chromosomal information, leading to an increased copy number of genes. Aneuploidy may be induced by stress conditions (UV exposure, antifungal drugs) [ 47 , 48 ]. Changes may be produced by different growth conditions, for example, in vivo exposure of Candida inducing highly variable isolates as compared to its in vitro exposure [ 30 ].…”

Section: The Virulence Of Candida Sppmentioning

confidence: 99%

“…This does not necessarily mean that heterozygous genes are non-functional, as many genes that present SNPs that encode stop codons are actually functional. LoH could reflect resistance to fluconazole or phenotypic changes (grey colonies with a lower chance of being phagocytized by macrophages and neutrophils and better fitness for colonizing the host) [ 47 , 49 ]. The LoH rate is variable and increases under the stress of external factors such as antifungal drugs or increased temperature [ 30 ].…”

Section: The Virulence Of Candida Sppmentioning

confidence: 99%

Candida and Candidiasis—Opportunism Versus Pathogenicity: A Review of the Virulence Traits

et al. 2020

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One of the most important questions in microbiology nowadays, is how apparently harmless, commensal yeasts like Candida spp. can cause a rising number of infections. The occurrence of the disease requires firstly the attachment to the host cells, followed by the invasion of the tissue. The adaptability translates into a rapid ability to respond to stress factors, to take up nutrients or to multiply under different conditions. By forming complex intracellular networks such as biofilms, Candida spp. become not only more refractive to antifungal therapies but also more prone to cause disease. The inter-microbial interactions can enhance the virulence of a strain. In vivo, the fungal cells face a multitude of challenges and, as a result, they develop complex strategies serving one ultimate goal: survival. This review presents the virulence factors of the most important Candida spp., contributing to a better understanding of the onset of candidiasis and raising awareness of the highly complex interspecies interactions that can change the outcome of the disease.

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The Impact of Gene Dosage and Heterozygosity on the Diploid Pathobiont Candida albicans

Cited by 26 publications

References 134 publications

Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across Candida albicans Strains and Ploidy States

Host-Induced Genome Instability Rapidly Generates Phenotypic Variation across Candida albicans Strains and Ploidy States

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

Candida and Candidiasis—Opportunism Versus Pathogenicity: A Review of the Virulence Traits

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