A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts

ABSTRACT The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal in...

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Autores principales:	Dorian J. Feistel, Rema Elmostafa, Nancy Nguyen, McKenna Penley, Levi Morran, Meleah A. Hickman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Caenorhabditis elegans Candida albicans host fitness immune function non-albicans Candida virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f083690bdbfb4ec8956f7bc5e0ca0224
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spelling	oai:doaj.org-article:f083690bdbfb4ec8956f7bc5e0ca02242021-11-15T15:22:22ZA Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts10.1128/mSphere.00697-182379-5042https://doaj.org/article/f083690bdbfb4ec8956f7bc5e0ca02242019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00697-18https://doaj.org/toc/2379-5042ABSTRACT The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that, in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence. IMPORTANCE Opportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found that Candida species, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.Dorian J. FeistelRema ElmostafaNancy NguyenMcKenna PenleyLevi MorranMeleah A. HickmanAmerican Society for MicrobiologyarticleCaenorhabditis elegansCandida albicanshost fitnessimmune functionnon-albicans CandidavirulenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caenorhabditis elegans Candida albicans host fitness immune function non-albicans Candida virulence Microbiology QR1-502
spellingShingle	Caenorhabditis elegans Candida albicans host fitness immune function non-albicans Candida virulence Microbiology QR1-502 Dorian J. Feistel Rema Elmostafa Nancy Nguyen McKenna Penley Levi Morran Meleah A. Hickman A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
description	ABSTRACT The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that, in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence. IMPORTANCE Opportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found that Candida species, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.
format	article
author	Dorian J. Feistel Rema Elmostafa Nancy Nguyen McKenna Penley Levi Morran Meleah A. Hickman
author_facet	Dorian J. Feistel Rema Elmostafa Nancy Nguyen McKenna Penley Levi Morran Meleah A. Hickman
author_sort	Dorian J. Feistel
title	A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
title_short	A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
title_full	A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
title_fullStr	A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
title_full_unstemmed	A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts
title_sort	novel virulence phenotype rapidly assesses <italic toggle="yes">candida</italic> fungal pathogenesis in healthy and immunocompromised <italic toggle="yes">caenorhabditis elegans</italic> hosts
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/f083690bdbfb4ec8956f7bc5e0ca0224
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A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> Hosts

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