title: β-glucan Exposure on the Fungal Cell Wall Tightly Correlates with Competitive Fitness ofCandidaSpecies in the Mouse Gastrointestinal Tract.
abstract: Candida albicansis 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 ofCandidaspecies and is a major source of systemic fungal infections. However, the factors that control GI colonization byCandidaspecies are not completely understood. We hypothesized that the fungal cell wall would play an important role in determining the competitive fitness ofCandidaspecies in the mammalian GI tract. To test this hypothesis, we generated a systematic collection of isogenicC. albicanscell 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-relatedCandidaspecies, 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 ofCandidastrains 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 within vitroandin vivovirulence. 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 limitCandidaGI fitness and hence represents a promising target to reduce fungal colonization in patients at risks of systemic candidiasis.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: XiaoHui
authors.initials: X
authors.lastname: Sem
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Giang T T
authors.initials: GT
authors.lastname: Le
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Alrina S M
authors.initials: AS
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Gloria
authors.initials: G
authors.lastname: Tso
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Marina
authors.initials: M
authors.lastname: Yurieva
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Webber W P
authors.initials: WW
authors.lastname: Liao
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lum
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Kandhadayar G
authors.initials: KG
authors.lastname: Srinivasan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research Singapore, Singapore.
authors.forename: Norman
authors.initials: N
authors.lastname: Pavelka
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000737:chemistry* / Q000254:growth & development*; D002473:Cell Wall / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D047071:beta-Glucans / Q000032:analysis*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1
keywords: Candida; Candida albicans; beta-glucan; cell wall; competitive fitness; dectin-1; gastrointestinal tract