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Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model

The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact wit...

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Autores principales: Romo, Jesús A., Tomihiro, Makenzie, Kumamoto, Carol A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449511/
https://www.ncbi.nlm.nih.gov/pubmed/37358292
http://dx.doi.org/10.1128/msphere.00122-23
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author Romo, Jesús A.
Tomihiro, Makenzie
Kumamoto, Carol A.
author_facet Romo, Jesús A.
Tomihiro, Makenzie
Kumamoto, Carol A.
author_sort Romo, Jesús A.
collection PubMed
description The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact with the gut microbiome and pathogenic microorganisms. Therefore, Candida species could be expected to play important ecological roles in the host gastrointestinal tract. Previously, our group demonstrated that pre-colonization of mice with C. albicans protected them against lethal C. difficile infection (CDI). Here, we show that mice pre-colonized with C. glabrata succumbed to CDI more rapidly than mice that were not pre-colonized suggesting an enhancement in C. difficile pathogenesis. Further, when C. difficile was added to pre-formed C. glabrata biofilms, an increase in matrix and overall biomass was observed. These effects were also shown with C. glabrata clinical isolates. Interestingly, the presence of C. difficile increased C. glabrata biofilm susceptibility to caspofungin, indicating potential effects on the fungal cell wall. Defining this intricate and intimate relationship will lead to an understanding of the role of Candida species in the context of CDI and novel aspects of Candida biology. IMPORTANCE: Most microbiome studies have only considered the bacterial populations while ignoring other members of the microbiome such as fungi, other eukaryotic microorganisms, and viruses. Therefore, the role of fungi in human health and disease has been significantly understudied compared to their bacterial counterparts. This has generated a significant gap in knowledge that has negatively impacted disease diagnosis, understanding, and the development of therapeutics. With the development of novel technologies, we now have an understanding of mycobiome composition, but we do not understand the roles of fungi in the host. Here, we present findings showing that Candida glabrata, an opportunistic pathogenic yeast that colonizes the mammalian gastrointestinal tract, can impact the severity and outcome of a Clostridioides difficile infection (CDI) in a murine model. These findings bring attention to fungal colonizers during CDI, a bacterial infection of the gastrointestinal tract.
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spelling pubmed-104495112023-08-25 Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model Romo, Jesús A. Tomihiro, Makenzie Kumamoto, Carol A. mSphere Research Article The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact with the gut microbiome and pathogenic microorganisms. Therefore, Candida species could be expected to play important ecological roles in the host gastrointestinal tract. Previously, our group demonstrated that pre-colonization of mice with C. albicans protected them against lethal C. difficile infection (CDI). Here, we show that mice pre-colonized with C. glabrata succumbed to CDI more rapidly than mice that were not pre-colonized suggesting an enhancement in C. difficile pathogenesis. Further, when C. difficile was added to pre-formed C. glabrata biofilms, an increase in matrix and overall biomass was observed. These effects were also shown with C. glabrata clinical isolates. Interestingly, the presence of C. difficile increased C. glabrata biofilm susceptibility to caspofungin, indicating potential effects on the fungal cell wall. Defining this intricate and intimate relationship will lead to an understanding of the role of Candida species in the context of CDI and novel aspects of Candida biology. IMPORTANCE: Most microbiome studies have only considered the bacterial populations while ignoring other members of the microbiome such as fungi, other eukaryotic microorganisms, and viruses. Therefore, the role of fungi in human health and disease has been significantly understudied compared to their bacterial counterparts. This has generated a significant gap in knowledge that has negatively impacted disease diagnosis, understanding, and the development of therapeutics. With the development of novel technologies, we now have an understanding of mycobiome composition, but we do not understand the roles of fungi in the host. Here, we present findings showing that Candida glabrata, an opportunistic pathogenic yeast that colonizes the mammalian gastrointestinal tract, can impact the severity and outcome of a Clostridioides difficile infection (CDI) in a murine model. These findings bring attention to fungal colonizers during CDI, a bacterial infection of the gastrointestinal tract. American Society for Microbiology 2023-06-26 /pmc/articles/PMC10449511/ /pubmed/37358292 http://dx.doi.org/10.1128/msphere.00122-23 Text en Copyright © 2023 Romo et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Romo, Jesús A.
Tomihiro, Makenzie
Kumamoto, Carol A.
Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title_full Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title_fullStr Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title_full_unstemmed Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title_short Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model
title_sort pre-colonization with the fungus candida glabrata exacerbates infection by the bacterial pathogen clostridioides difficile in a murine model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449511/
https://www.ncbi.nlm.nih.gov/pubmed/37358292
http://dx.doi.org/10.1128/msphere.00122-23
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