Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis

ABSTRACT Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, w...

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Autores principales:	M. Bertolini, R. Vazquez Munoz, L. Archambault, S. Shah, J. G. S. Souza, R. C. Costa, A. Thompson, Y. Zhou, T. Sobue, A. Dongari-Bagtzoglou
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Candida albicans oral microbiome pathogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c7c595b03204bc6aa5afe300fd5a5d7
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spelling	oai:doaj.org-article:1c7c595b03204bc6aa5afe300fd5a5d72021-11-10T18:37:52ZMucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis10.1128/mBio.01937-212150-7511https://doaj.org/article/1c7c595b03204bc6aa5afe300fd5a5d72021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01937-21https://doaj.org/toc/2150-7511ABSTRACT Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, we hypothesized that changes in the abundance or composition of the mucosal bacterial microbiota induced by dietary sucrose during the development of OPC can modulate C. albicans virulence. C. albicans burdens and mucosal lesions were evaluated in a mouse cortisone immunosuppression model amended with sucrose. We also analyzed the mucosal bacterial composition using 16S rRNA gene sequencing and culture methods. In immunocompetent mice, sucrose significantly increased total bacterial burdens and reduced alpha diversity, by increasing the relative abundance of mitis group streptococci. In immunocompromised mice, C. albicans infection was associated with a significantly reduced bacterial alpha diversity due to an increase in the relative abundance of enterococci. When exposed to dietary sucrose, these mice had reduced C. albicans burdens and reduced bacterial alpha diversity, associated with an increase in the relative abundance of Lactobacillus. SparCC correlation networks showed a significant negative correlation between Lactobacillus and Enterococcus in all Candida-infected mice. Depletion of lactobacilli with antibiotic treatment partially restored C. albicans burdens in mice receiving sucrose. In coculture in vitro experiments, mouse oral Lactobacillus johnsonii isolates inhibited growth of Enterococcus faecalis isolates and C. albicans. These results support the hypothesis that the sucrose-induced attenuation of C. albicans virulence was a result of changes in the mucosal bacterial microbiome characterized by a reduction in enterococci and an increase in lactobacilli. IMPORTANCE By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans, and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease. We also showed that Lactobacillus johnsonii may curtail Candida virulence both by inhibiting its growth and by inhibiting the growth of potentially synergistic bacteria such as enterococci. Our results support the concept that Candida pathogenesis should be viewed in the contexts of both a susceptible host and a mucosal bacterial microbiota conducive to virulence.M. BertoliniR. Vazquez MunozL. ArchambaultS. ShahJ. G. S. SouzaR. C. CostaA. ThompsonY. ZhouT. SobueA. Dongari-BagtzoglouAmerican Society for MicrobiologyarticleCandida albicansoral microbiomepathogenesisMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans oral microbiome pathogenesis Microbiology QR1-502
spellingShingle	Candida albicans oral microbiome pathogenesis Microbiology QR1-502 M. Bertolini R. Vazquez Munoz L. Archambault S. Shah J. G. S. Souza R. C. Costa A. Thompson Y. Zhou T. Sobue A. Dongari-Bagtzoglou Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
description	ABSTRACT Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, we hypothesized that changes in the abundance or composition of the mucosal bacterial microbiota induced by dietary sucrose during the development of OPC can modulate C. albicans virulence. C. albicans burdens and mucosal lesions were evaluated in a mouse cortisone immunosuppression model amended with sucrose. We also analyzed the mucosal bacterial composition using 16S rRNA gene sequencing and culture methods. In immunocompetent mice, sucrose significantly increased total bacterial burdens and reduced alpha diversity, by increasing the relative abundance of mitis group streptococci. In immunocompromised mice, C. albicans infection was associated with a significantly reduced bacterial alpha diversity due to an increase in the relative abundance of enterococci. When exposed to dietary sucrose, these mice had reduced C. albicans burdens and reduced bacterial alpha diversity, associated with an increase in the relative abundance of Lactobacillus. SparCC correlation networks showed a significant negative correlation between Lactobacillus and Enterococcus in all Candida-infected mice. Depletion of lactobacilli with antibiotic treatment partially restored C. albicans burdens in mice receiving sucrose. In coculture in vitro experiments, mouse oral Lactobacillus johnsonii isolates inhibited growth of Enterococcus faecalis isolates and C. albicans. These results support the hypothesis that the sucrose-induced attenuation of C. albicans virulence was a result of changes in the mucosal bacterial microbiome characterized by a reduction in enterococci and an increase in lactobacilli. IMPORTANCE By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans, and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease. We also showed that Lactobacillus johnsonii may curtail Candida virulence both by inhibiting its growth and by inhibiting the growth of potentially synergistic bacteria such as enterococci. Our results support the concept that Candida pathogenesis should be viewed in the contexts of both a susceptible host and a mucosal bacterial microbiota conducive to virulence.
format	article
author	M. Bertolini R. Vazquez Munoz L. Archambault S. Shah J. G. S. Souza R. C. Costa A. Thompson Y. Zhou T. Sobue A. Dongari-Bagtzoglou
author_facet	M. Bertolini R. Vazquez Munoz L. Archambault S. Shah J. G. S. Souza R. C. Costa A. Thompson Y. Zhou T. Sobue A. Dongari-Bagtzoglou
author_sort	M. Bertolini
title	Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
title_short	Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
title_full	Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
title_fullStr	Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
title_full_unstemmed	Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis
title_sort	mucosal bacteria modulate <named-content content-type="genus-species">candida albicans</named-content> virulence in oropharyngeal candidiasis
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/1c7c595b03204bc6aa5afe300fd5a5d7
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Mucosal Bacteria Modulate <named-content content-type="genus-species">Candida albicans</named-content> Virulence in Oropharyngeal Candidiasis

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