A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection
Opportunistic pathogens are a major threat to people, especially those with impaired immune systems. Two of the most important microbes in this category are the fungus Candida albicans and Gram-positive bacteria of the genus Enterococcus, which share overlapping niches in the oral cavity, gastrointe...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1467896/full |
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| author | Raja Veerapandian Anuja Paudyal Sarah M. Schneider Sonny T. M. Lee Govindsamy Vediyappan Govindsamy Vediyappan |
| author_facet | Raja Veerapandian Anuja Paudyal Sarah M. Schneider Sonny T. M. Lee Govindsamy Vediyappan Govindsamy Vediyappan |
| author_sort | Raja Veerapandian |
| collection | DOAJ |
| description | Opportunistic pathogens are a major threat to people, especially those with impaired immune systems. Two of the most important microbes in this category are the fungus Candida albicans and Gram-positive bacteria of the genus Enterococcus, which share overlapping niches in the oral cavity, gastrointestinal and urogenital tracts. The clinical importance of oral C. albicans biofilm and its interaction with the host under immunosuppressive conditions remains largely understudied. Here, we used a mouse model of oropharyngeal candidiasis (OPC) with cortisone acetate injection on alternate days and a continuous supply of C. albicans in drinking water for three days, resulting in immunosuppression. Results showed abundant growth of resident oral bacteria and a strong C. albicans biofilm on the tongue consisting of hyphae which damaged papillae, the epidermal layer, and invaded tongue tissue with the accumulation of inflammatory cells as demonstrated by Grocott’s methenamine silver and hematoxylin and eosin staining, respectively. The dispersed microbes from the oral biofilm colonized the gastrointestinal (GI) tract and damaged its integrity, disseminating microbes to other organs. Although no visible damage was observed in the kidney and liver, except increased lipid vacuoles in the liver cells, C. albicans was found in the liver homogenate. Intriguingly, we found co-occurrence of Enterococcus faecalis in the tongue, liver, and stool of immunosuppressed control and C. albicans infected organs. Targeted 16S rRNA and ITS2 amplicon sequencing of microbes from the fecal samples of mice confirmed the above results in the stool samples and revealed an inverse correlation of beneficial microbes in the dysbiosis condition. Our study shows that mucosal-oral infection of C. albicans under immunosuppressed conditions causes tissue damage and invasion in local and distant organs; the invasion may be aided by the overgrowth of the resident endogenous Enterobacteriaceae and other members, including the opportunistic pathogen Enterococcus faecalis. |
| format | Article |
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| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-cc940bef7cc643c0a1ce69b0786127df2025-01-20T05:23:39ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.14678961467896A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infectionRaja Veerapandian0Anuja Paudyal1Sarah M. Schneider2Sonny T. M. Lee3Govindsamy Vediyappan4Govindsamy Vediyappan5Division of Biology, Kansas State University, Manhattan, KS, United StatesDivision of Biology, Kansas State University, Manhattan, KS, United StatesDiagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS, United StatesDivision of Biology, Kansas State University, Manhattan, KS, United StatesDivision of Biology, Kansas State University, Manhattan, KS, United StatesDiagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS, United StatesOpportunistic pathogens are a major threat to people, especially those with impaired immune systems. Two of the most important microbes in this category are the fungus Candida albicans and Gram-positive bacteria of the genus Enterococcus, which share overlapping niches in the oral cavity, gastrointestinal and urogenital tracts. The clinical importance of oral C. albicans biofilm and its interaction with the host under immunosuppressive conditions remains largely understudied. Here, we used a mouse model of oropharyngeal candidiasis (OPC) with cortisone acetate injection on alternate days and a continuous supply of C. albicans in drinking water for three days, resulting in immunosuppression. Results showed abundant growth of resident oral bacteria and a strong C. albicans biofilm on the tongue consisting of hyphae which damaged papillae, the epidermal layer, and invaded tongue tissue with the accumulation of inflammatory cells as demonstrated by Grocott’s methenamine silver and hematoxylin and eosin staining, respectively. The dispersed microbes from the oral biofilm colonized the gastrointestinal (GI) tract and damaged its integrity, disseminating microbes to other organs. Although no visible damage was observed in the kidney and liver, except increased lipid vacuoles in the liver cells, C. albicans was found in the liver homogenate. Intriguingly, we found co-occurrence of Enterococcus faecalis in the tongue, liver, and stool of immunosuppressed control and C. albicans infected organs. Targeted 16S rRNA and ITS2 amplicon sequencing of microbes from the fecal samples of mice confirmed the above results in the stool samples and revealed an inverse correlation of beneficial microbes in the dysbiosis condition. Our study shows that mucosal-oral infection of C. albicans under immunosuppressed conditions causes tissue damage and invasion in local and distant organs; the invasion may be aided by the overgrowth of the resident endogenous Enterobacteriaceae and other members, including the opportunistic pathogen Enterococcus faecalis.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1467896/fulloropharyngeal candidiasisCandida albicansmice modelimmunosuppressiongut microbiomeEnterococcus |
| spellingShingle | Raja Veerapandian Anuja Paudyal Sarah M. Schneider Sonny T. M. Lee Govindsamy Vediyappan Govindsamy Vediyappan A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection Frontiers in Cellular and Infection Microbiology oropharyngeal candidiasis Candida albicans mice model immunosuppression gut microbiome Enterococcus |
| title | A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection |
| title_full | A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection |
| title_fullStr | A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection |
| title_full_unstemmed | A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection |
| title_short | A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection |
| title_sort | mouse model of immunosuppression facilitates oral candida albicans biofilms bacterial dysbiosis and dissemination of infection |
| topic | oropharyngeal candidiasis Candida albicans mice model immunosuppression gut microbiome Enterococcus |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1467896/full |
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