A novel virulence phenotype rapidly assesses Candida fungal pathogenesis in healthy and immunocompromised Caenorhabditis elegans hosts

• Type of Material: Article
• Authors: Dorian J. Feistel, Emory University; Rema Elmostafa, Emory University; Nancy Nguyen, Emory University; McKenna Penley, Emory University; Levi Morran, Emory University; Meleah A. Hickman, Emory University
• Language: English
• Date: 2019-03-01
• Publisher: American Society for Microbiology: Open Access Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Feistel et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/mSphere.00697-18
• Title of Journal or Parent Work: mSphere
• ISSN: 2379-5042
• Volume: 4
• Issue: 2
• Keywords: immune function; Candida; Host-Pathogen Interactions; Animals; host fitness; Virulence; Phenotype; Immunity, Innate; Reproduction; Fungal Proteins; virulence; Candida albicans; Caenorhabditis elegans; Candidiasis; Immunocompromised Host; Survival Analysis; non-albicans Candida
• Research Categories: Biology, General; Biology, Microbiology

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.