Candida albicans Isolates 529L and CHN1 Exhibit Stable Colonization of the Murine Gastrointestinal Tract

Autor: Pallavi Kakade, Animesh Mishra, Swathi Penumutchu, Iuliana V. Ene, Shen-Huan Liang, Richard J. Bennett, Nicholas L. Tosini, Corrine Maufrais, Tobias M. Hohl, Peter Belenky, Ying Taur, Andrew Y. Koh, Liam D McDonough, Bing Zhai
Přispěvatelé: Brown University, Yale University School of Medicine, University of Texas Southwestern Medical Center [Dallas], Memorial Sloan Kettering Cancer Center (MSKCC), Département de Mycologie - Department of Mycology, Institut Pasteur [Paris], Weill Medical College of Cornell University [New York], This work was supported by National Institutes of Health (NIH) grants R01 AI093808 (TMH), R01 AI139632 (TMH), R21 AI105617 (TMH), R21 AI156157 (TMH), Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases Award (TMH), Ludwig Center for Cancer Immunotherapy (TMH), NIH P30 CA008748 (to MSKCC), NIH R01 AI123163 (AYK), K24 AI150992 (AYK), Roberta I. and Normal L. Pollock Fund (AYK), NIH R01 AI41893 (RJB), NIH R01 AI081704 (RJB), NIH R21 AI144651 (RJB), NIH R21 AI139592 (IVE), NIH NIGMS IDeA award P20GM109035 (IVE), Institut Pasteur G5 (IVE), CIFAR Azrieli Global Scholar Award (IVE), NIH NCCIH R21AT010366 (PB), NIDDK R01 DK125382 (PB) and NSF Graduate Research Fellowship award 1644760 (SP)., Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: mBio, Vol 12, Iss 6 (2021)
mBio
Microbial Pathogenesis
Microbial Pathogenesis, 2021, 12 (6), pp.e02878-21. ⟨10.1128/mBio.02878-21⟩
ISSN: 2150-7511
0882-4010
1096-1208
Popis: Candida albicans is a pathobiont that colonizes multiple niches in the body including the gastrointestinal (GI) tract, but is also responsible for both mucosal and systemic infections. Despite its prevalence as a human commensal, the murine GI tract is generally refractory to colonization with the C. albicans reference isolate SC5314. Here, we identify two C. albicans isolates, 529L and CHN1, that stably colonize the murine GI tract in three different animal facilities under conditions where SC5314 is lost from this niche. Analysis of the bacterial microbiota did not show notable differences between mice colonized with the three C. albicans strains. We compared the genotypes and phenotypes of these three strains and identified thousands of SNPs and multiple phenotypic differences, including their ability to grow and filament in response to nutritional cues. Despite striking filamentation differences under laboratory conditions, however, analysis of cell morphology in the GI tract revealed that the three isolates exhibited similar filamentation properties in this in vivo niche. Notably, we found that SC5314 is more sensitive to the antimicrobial peptide CRAMP, and the use of CRAMP-deficient mice increased the ability of SC5314 to colonize the GI tract relative to CHN1 and 529L. These studies provide new insights into how strain-specific differences impact C. albicans traits in the host and advance CHN1 and 529L as relevant strains to study C. albicans pathobiology in its natural host niche.IMPORTANCEUnderstanding how fungi colonize the GI tract is increasingly recognized as highly relevant to human health. The animal models used to study Candida albicans commensalism commonly rely on altering the host microbiome (via antibiotic treatment or defined diets) to establish successful GI colonization by the C. albicans reference isolate SC5314. Here, we characterize two C. albicans isolates that can colonize the murine GI tract without antibiotic treatment and can therefore be used as tools for studying fungal commensalism. Importantly, experiments were replicated in three different animal facilities and utilized three different mouse strains. Differential colonization between fungal isolates was not associated with alterations in the bacterial microbiome but rather with distinct responses to CRAMP, a host antimicrobial peptide. This work emphasizes the importance of C. albicans intra-species variation as well as host anti-microbial defense mechanisms in defining commensal interactions.
Databáze: OpenAIRE
Externí odkaz: