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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-04-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00697-18 |
| _version_ | 1818836599136321536 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:09:10Z |
| format | Article |
| id | doaj.art-f083690bdbfb4ec8956f7bc5e0ca0224 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T03:09:10Z |
| publishDate | 2019-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-f083690bdbfb4ec8956f7bc5e0ca02242022-12-21T20:38:03ZengAmerican Society for MicrobiologymSphere2379-50422019-04-014210.1128/mSphere.00697-18A Novel Virulence Phenotype Rapidly Assesses <italic toggle="yes">Candida</italic> Fungal Pathogenesis in Healthy and Immunocompromised <italic toggle="yes">Caenorhabditis elegans</italic> HostsDorian J. Feistel0Rema Elmostafa1Nancy Nguyen2McKenna Penley3Levi Morran4Meleah A. Hickman5Department of Biology, Emory University, Atlanta, Georgia, USADepartment of Biology, Emory University, Atlanta, Georgia, USADepartment of Biology, Emory University, Atlanta, Georgia, USADepartment of Biology, Emory University, Atlanta, Georgia, USADepartment of Biology, Emory University, Atlanta, Georgia, USADepartment of Biology, Emory University, Atlanta, Georgia, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00697-18Caenorhabditis elegansCandida albicanshost fitnessimmune functionnon-albicans Candidavirulence |
| spellingShingle | 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 mSphere Caenorhabditis elegans Candida albicans host fitness immune function non-albicans Candida virulence |
| 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_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_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_sort | novel virulence phenotype rapidly assesses italic toggle yes candida italic fungal pathogenesis in healthy and immunocompromised italic toggle yes caenorhabditis elegans italic hosts |
| topic | Caenorhabditis elegans Candida albicans host fitness immune function non-albicans Candida virulence |
| url | https://journals.asm.org/doi/10.1128/mSphere.00697-18 |
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