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

mBio

Andrew Y. Koh¹  Animesh A. Mishra¹  Swathi Penumutchu²  Shen-Huan Liang²  Iuliana V. Ene²  Pallavi Kakade²  Peter Belenky²  Liam D. McDonough²  Richard J. Bennett²  Corrine Maufrais³  Ying Taur⁴  Bing Zhai⁴  Nicholas Tosini⁴  Tobias M. Hohl⁴ 

[1] Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, USA;Department of Mycology, Institut Pasteur, Paris, France;Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA;

关键词: fungal biology;    gastrointestinal colonization;    microbiome;    strain diversity;   

DOI  :  10.1128/mBio.02878-21

来源: DOAJ

【 摘 要 】

ABSTRACT 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 among mice colonized with the three C. albicans strains. We compared the genotypes and phenotypes of these three strains and identified thousands of single nucleotide polymorphisms (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 modestly 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. IMPORTANCE Understanding 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 intraspecies variation as well as host antimicrobial defense mechanisms in defining the outcome of commensal interactions.

【 授权许可】

Unknown