AUTHOR=Das Diprasom , HogenEsch Harm , Thangamani Shankar 

TITLE=Intestinal colonization with Candida auris and mucosal immune response in mice treated with cefoperazone oral antibiotic

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1123200

DOI=10.3389/fimmu.2023.1123200

ISSN=1664-3224

ABSTRACT=<p><italic>Candida auris</italic>, an emerging multi-drug resistant fungal pathogen, causes invasive infections in humans. The factors regulating the colonization of <italic>C. auris</italic> in host niches are not well understood. In this study, we examined the effect of antibiotic-induced gut dysbiosis on <italic>C. auris</italic> intestinal colonization, dissemination, microbiome composition and the mucosal immune response. Our results indicate that mice treated with cefoperazone alone had a significant increase in <italic>C. auris</italic> intestinal colonization compared to untreated control groups. A significant increase in the dissemination of <italic>C. auris</italic> from the intestine to internal organs was observed in antibiotic-treated immunosuppressed mice. Intestinal colonization of <italic>C. auris</italic> alters the microbiome composition of antibiotic-treated mice. Relative abundance of firmicutes members mainly <italic>Clostridiales</italic> and <italic>Paenibacillus</italic> were considerably increased in the cefoperazone-treated mice infected with <italic>C. auris</italic> compared to cefoperazone-treated uninfected mice. Next, we examined the mucosal immune response of <italic>C. auris</italic> infected mice and compared the results with <italic>Candida albicans</italic> infection. The number of CD11b+ CX3CR1+ macrophages was significantly decreased in the intestine of <italic>C. auris</italic> infected mice when compared to <italic>C. albicans</italic> infection. On the other hand, both <italic>C. auris</italic> and <italic>C. albicans</italic> infected mice had a comparable increase of the number of Th17 and Th22 cells in the intestine. A significant increase in <italic>Candida</italic>-specific IgA was observed in the serum of <italic>C. auris</italic> but not in the <italic>C. albicans</italic> infected mice. Taken together, treatment with broad-spectrum antibiotic increased the colonization and dissemination of <italic>C. auris</italic> from the intestine. Furthermore, findings from this study for the first time revealed the microbiome composition, innate and adaptive cellular immune response to intestinal infection with <italic>C. auris</italic>.</p>