Please use this identifier to cite or link to this item: https://doi.org/10.3389/fcimb.2016.00186
Title: β-glucan exposure on the fungal cell wall tightly correlates with competitive fitness of Candida species in the mouse gastrointestinal tract
Authors: Sem, X
Le, G.T.T
Tan, A.S.M
Tso, G
Yurieva, M
Liao, W.W.P
Lum, J
Srinivasan, K.G
Poidinger, M 
Zolezzi, F
Pavelka, N
Keywords: beta glucan
dectin 1
genomic DNA
beta glucan
dectin 1
lectin
Article
candidiasis
controlled study
female
flow cytometry
fungal cell wall
fungal colonization
fungal virulence
gastrointestinal infection
gene mutation
homozygosity
macrophage
mouse
nonhuman
phagocytosis
phenotype
quantitative assay
sequence analysis
animal
Candida albicans
cell wall
chemistry
gastrointestinal tract
growth, development and aging
metabolism
microbiology
Animals
beta-Glucans
Candida albicans
Cell Wall
Gastrointestinal Tract
Lectins, C-Type
Mice
Issue Date: 2016
Citation: Sem, X, Le, G.T.T, Tan, A.S.M, Tso, G, Yurieva, M, Liao, W.W.P, Lum, J, Srinivasan, K.G, Poidinger, M, Zolezzi, F, Pavelka, N (2016). β-glucan exposure on the fungal cell wall tightly correlates with competitive fitness of Candida species in the mouse gastrointestinal tract. Frontiers in Cellular and Infection Microbiology 6 (DEC) : 186. ScholarBank@NUS Repository. https://doi.org/10.3389/fcimb.2016.00186
Rights: Attribution 4.0 International
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. © 2016 Sem, Le, Tan, Tso, Yurieva, Liao, Lum, Srinivasan, Poidinger, Zolezzi and Pavelka.
Source Title: Frontiers in Cellular and Infection Microbiology
URI: https://scholarbank.nus.edu.sg/handle/10635/183359
ISSN: 22352988
DOI: 10.3389/fcimb.2016.00186
Rights: Attribution 4.0 International
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