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

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 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.

Human commensalCandida albicansstrains demonstrate substantial within-host diversity and retained pathogenic potential

“…The five slowest-growing strains originated from five different hosts and showed significantly decreased growth rate and saturating density relative to other isolates from the same host. Although the five slowest-growing isolates were all obtained from oral samples, we did not observe a significant difference in growth rate between oral and fecal samples As filamentation has been tightly associated with virulence, and because previous work in murine models has suggested that gut adapted strains may lose their ability to filament [20,34,36], we examined each isolate in the collection for their ability to form hyphae using 10% serum and febrile temperatures as two inducing cues.…”

“…We then performed growth assays on all 910 isolates and the SC5314 reference strain in rich medium (yeast peptone) with dextrose, galactose, or glycerol as the carbon source. We observed unimodal distributions with a long tail of slow-growing strains for both exponential growth (µ max ) and saturating density (K) in rich media (Fig 1C As filamentation has been tightly associated with virulence, and because previous work in murine models has suggested that gut adapted strains may lose their ability to filament [20,34,36], we examined each isolate in the collection for their ability to form hyphae using 10% serum and febrile temperatures as two inducing cues.…”

“…As filamentation has been tightly associated with virulence, and because previous work in murine models has suggested that gut adapted strains may lose their ability to filament [20,34,36], we examined each isolate in the collection for their ability to form hyphae using 10% serum and febrile temperatures as two inducing cues. Additionally, we examined the morphology of each strain under the non-inducing condition of YPD at 30°C to identify constitutive filamentation, as has been observed from isolates collected from sputum samples from cystic fibrosis patients [44].…”

“…In the model yeast Saccharomyces cerevisiae, there is extensive variability in genotype and phenotype among different isolates that has been linked to the ability of S. cerevisiae to adapt to a wide range of environmental conditions [15, 16]. Recent work has highlighted intra-species variation in important aspects of C. albicans biology [17–20]. There are currently 17 clades of C. albicans, which were initially defined through multilocus sequence typing (MLST) [21–23].…”

“…In oral candidiasis, trisomic strains have been identified with a commensal phenotype [41]. Additionally, the 529L strain of C. albicans causes less damage and inflammation during oropharyngeal candidiasis [42], and persists at a higher fungal burden in both the mouth and the gut [20]. These potentially divergent selection pressures imply that commensal C. albicans strains can differ from isolates that cause invasive disease, but the genetic determinants underlying this difference have not been defined.…”