title: Murine model of dextran sulfate sodium-induced colitis reveals Candida glabrata virulence and contribution of β-mannosyltransferases.
abstract: Candida glabrata, like Candida albicans, is an opportunistic yeast pathogen that has adapted to colonize all segments of the human gastrointestinal tract and vagina. The C. albicans cell wall expresses β-1,2-linked mannosides (β-Mans), promoting its adherence to host cells and tissues. Because β-Mans are also present in C. glabrata, their role in C. glabrata colonization and virulence was investigated in a murine model of dextran sulfate sodium (DSS)-induced colitis. Five clustered genes of C. glabrata encoding β-mannosyltransferases, BMT2-BMT6, were deleted simultaneously. β-Man expression was studied by Western blotting, flow cytometry, and NMR analysis. Mortality, clinical, histologic, and colonization scores were determined in mice receiving DSS and different C. glabrata strains. The results show that C. glabrata bmt2-6 strains had a significant reduction in β-1,2-Man expression and a disappearance of β-1,2-mannobiose in the acid-stable domain. A single gavage of C. glabrata wild-type strain in mice with DSS-induced colitis caused a loss of body weight, colonic inflammation, and mortality. Mice receiving C. glabrata bmt2-6 mutant strains had normal body weight and reduced colonic inflammation. Lower numbers of colonies of C. glabrata bmt2-6 were recovered from stools and different parts of the gastrointestinal tract. Histopathologic examination revealed that the wild-type strain had a greater ability to colonize tissue and cause tissue damage. These results showed that C. glabrata has a high pathogenic potential in DSS-induced colitis, where β-Mans contribute to colonization and virulence.
authors.affiliation: Université Lille Nord de France, 59000 Lille, France. jawhars@ccf.org
authors.forename: Samir
authors.initials: S
authors.lastname: Jawhara
authors.forename: Estelle
authors.initials: E
authors.lastname: Mogensen
authors.forename: François
authors.initials: F
authors.lastname: Maggiotto
authors.forename: Chantal
authors.initials: C
authors.lastname: Fradin
authors.forename: Aurore
authors.initials: A
authors.lastname: Sarazin
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maes
authors.forename: Yann
authors.initials: Y
authors.lastname: Guérardel
authors.forename: Guilhem
authors.initials: G
authors.lastname: Janbon
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
mesh_terms: D000818:Animals; D041221:Candida glabrata / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D003092:Colitis / Q000139:chemically induced* / Q000382:microbiology*; D003106:Colon / Q000382:microbiology; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000382:microbiology; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009844:Oligosaccharides / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D009844:Oligosaccharides; C028569:oligomannoside; D016264:Dextran Sulfate; D008364:Mannosyltransferases