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

Liam D Mcdonough,Corrine Maufrais,Shen-Huan Liang,Ying Taur,Pallavi Kakade,Andrew Y Koh,Swathi Penumutchu,Tobias M Hohl,Richard J Bennett,Nicholas Tosini,Iuliana V Ene,Peter Belenky,Bing Zhai,Animesh A Mishra

doi:10.1128/mbio.02878-21

Abstract

ABSTRACTCandida 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.

Highlights

The fungal component of the human microbiota, the mycobiota, is increasingly recognized as playing key roles in host homeostasis [1,2,3,4,5,6,7]
For C57BL/6J (RI, New York (NY)) mice, colonization differences between isolates were readily apparent in the first week post gavage and in the Rhode Island (RI) facility these differences increased out to 28 days of colonization (Figure 1A, B)
C. albicans is a prevalent commensal of the human GI tract and yet is absent from the GI tract of most laboratory mouse strains

Summary

Introduction

The fungal component of the human microbiota, the mycobiota, is increasingly recognized as playing key roles in host homeostasis [1,2,3,4,5,6,7]. A pathobiont that is found in over 70% of individuals, is a prominent member of the gastrointestinal (GI) mycobiota [8, 9]. This species is present in multiple niches of the human body and can cause a variety of opportunistic mucosal and systemic infections. C. albicans, as well as other Candida species, are linked to intestinal disease, with C. albicans consistently found at high levels in cohorts of. The loss of host signaling pathways involved in fungal recognition, such as those involving Dectin-1 or Dectin-3, may exacerbate colitis due to increased Candida levels in the gut [15, 16]

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Results

Conclusion