Year-end Sale % OFF 
Abstract
Candida albicans is responsible for ~400,000 systemic fungal infections annually, with an associated mortality rate of 46–75%. The human gastrointestinal (GI) tract represents the largest natural reservoir of Candida species and is a major source of systemic fungal infections. However, the factors that control GI colonization by Candida species are not completely understood. We hypothesized that the fungal cell wall would play an important role in determining the competitive fitness of Candida species in the mammalian GI tract. To test this hypothesis, we generated a systematic collection of isogenic C. albicans cell wall mutants and measured their fitness in the mouse GI tract via quantitative competition assays. Whereas a large variation in competitive fitness was found among mutants, no correlation was observed between GI fitness and total levels of individual cell wall components. Similar results were obtained in a set of distantly-related Candida species, suggesting that total amounts of individual cell wall components do not determine the ability of fungi to colonize the GI tract. We then subjected this collection of Candida strains and species to an extensive quantitative phenotypic profiling in search for features that might be responsible for their differences in GI fitness, but found no association with the ability to grow in GI-mimicking and stressful environments or with in vitro and in vivo virulence. The most significant association with GI fitness was found to be the strength of signaling through the Dectin-1 receptor. Using a quantitative assay to measure the amount of exposed β-glucan on the surface of fungal cells, we found this parameter, unlike total β-glucan levels, to be strongly predictive of competitive fitness in the mouse GI tract. These data suggest that fungal cell wall architecture, more so than its crude composition, critically determines the ability of fungi to colonize the mammalian GI tract. In particular, recognition of exposed β-glucan by Dectin-1 receptor appears to severely limit Candida GI fitness and hence represents a promising target to reduce fungal colonization in patients at risks of systemic candidiasis.
Highlights
The mammalian gastrointestinal (GI) tract is a complex environment hosting a large number and variety of microbes that include bacteria and fungi (Qin et al, 2010; Iliev et al, 2012)
Experiments critical for this study have been repeated in parallel using both mnt1/mnt1;mnt2/mnt2 strains and found not to lead to significantly different outcomes (Supplementary Figure 1). This collection of C. albicans cell wall mutants represents a carefully constructed isogenic set of strains that is well suited for quantitative phenotypic analyses without potential confounders due to undocumented genetic or karyotypic differences
Since these strains were generated without using any auxotrophic marker, they are expected to show no intrinsic deficiency in their ability to grow in nutrient-limited environments, e.g., during colonization or infection of certain host tissues, and should represent an invaluable resource to study the role of the C. albicans cell wall during interaction with the host
Summary
The mammalian gastrointestinal (GI) tract is a complex environment hosting a large number and variety of microbes that include bacteria and fungi (Qin et al, 2010; Iliev et al, 2012). While much effort has been placed in unraveling microbiota associations with host health and disease, little is known about factors that determine the ability of individual microbes, and especially fungi, to colonize the GI environment. The most frequently isolated fungi from the human GI tract belong to the Candida genus, with C. albicans consistently ranking as the most successful fungal colonizer in industrialized countries, followed by C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. dubliniensis (Maccallum, 2010). Understanding the factors that control the ability of Candida species to colonize the mammalian GI tract might open up opportunities for novel prevention strategies of systemic candidiasis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
