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Intestinal colonization with Candida auris and mucosal immune response in mice treated with cefoperazone oral
Diprasom Das1, Harm HogenEsch1,2, Shankar Thangamani1,2
1Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States.
Abstract:
Candida auris, an emerging multi-drug resistant fungal pathogen, causes invasive infections in humans. The factors regulating the colonization of C. auris in host niches are not well understood. In this study, we examined the effect of antibiotic-induced gut dysbiosis on C. auris intestinal colonization, dissemination, microbiome composition and the mucosal immune response. Our results indicate that mice treated with cefoperazone alone had a significant increase in C. auris intestinal colonization compared to untreated control groups. A significant increase in the dissemination of C. auris from the intestine to internal organs was observed in antibiotic-treated immunosuppressed mice. Intestinal colonization of C. auris alters the microbiome composition of antibiotic-treated mice. Relative abundance of firmicutes members mainly Clostridiales and Paenibacillus were considerably increased in the cefoperazone-treated mice infected with C. auris compared to cefoperazone-treated uninfected mice. Next, we examined the mucosal immune response of C. auris infected mice and compared the results with Candida albicans infection. The number of CD11b+ CX3CR1+ macrophages was significantly decreased in the intestine of C. auris infected mice when compared to C. albicans infection. On the other hand, both C. auris and C. albicans infected mice had a comparable increase of the number of Th17 and Th22 cells in the intestine. A significant increase in Candida-specific IgA was observed in the serum of C. auris but not in the C. albicans infected mice. Taken together, treatment with broad-spectrum antibiotic increased the colonization and dissemination of C. auris 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 C. auris.
Insights
Antibiotic-induced gut dysbiosis significantly increases intestinal colonization and dissemination of the multi-drug resistant fungus Candida auris. This study reveals key changes in the gut microbiome and immune responses to C. auris infection.
Area of Science:
- Mycology
- Immunology
- Microbiome Research
Background:
- Candida auris is an emerging multi-drug resistant fungal pathogen causing invasive infections.
- Understanding C. auris colonization factors in host niches is crucial.
- Gut dysbiosis is implicated in various infections, but its role in C. auris pathogenesis is unclear.
Purpose of the Study:
- To investigate the impact of antibiotic-induced gut dysbiosis on C. auris intestinal colonization and dissemination.
- To analyze alterations in gut microbiome composition during C. auris infection.
- To characterize the mucosal immune response to C. auris compared to Candida albicans.
Main Methods:
- Mice were treated with cefoperazone to induce gut dysbiosis.
- C. auris intestinal colonization and dissemination to internal organs were assessed.
- Gut microbiome composition was analyzed using 16S rRNA sequencing.
- Innate and adaptive immune cell populations (macrophages, Th17, Th22) and IgA levels were measured.
Main Results:
- Cefoperazone treatment significantly increased C. auris intestinal colonization.
- Antibiotic-treated immunosuppressed mice showed increased dissemination of C. auris to internal organs.
- C. auris infection altered the gut microbiome, increasing the relative abundance of Firmicutes (Clostridiales, Paenibacillus).
- CD11b+ CX3CR1+ macrophages decreased in C. auris infected mice compared to C. albicans.
- Th17 and Th22 cell populations increased comparably in both C. auris and C. albicans infections.
- Candida-specific IgA increased in serum of C. auris infected mice.
Conclusions:
- Broad-spectrum antibiotic treatment promotes C. auris intestinal colonization and dissemination.
- C. auris infection significantly impacts gut microbiome composition.
- This study provides novel insights into the innate and adaptive immune responses to intestinal C. auris infection.
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