title: Role of capsular modified heptose in the virulence of Campylobacter jejuni.
abstract: The Campylobacter jejuni capsular polysaccharide is important for virulence and often contains a modified heptose. In strain ATCC 700819 (a.k.a. NCTC 11168), the modified heptose branches off from the capsular backbone and is directly exposed to the environment. We reported previously that the enzymes encoded by wcaG, mlghB and mlghC are involved in heptose modification. Here, we show that inactivation of any of these genes leads to production of capsule lacking modified heptose and alters the transcription of other capsule modification genes differentially. Inactivation of mlghB or mlghC, but not of wcaG, decreased susceptibility to bile salts and abrogated invasion of intestinal cells. All mutants showed increased sensitivity to serum killing, especially wcaG::cat, and had defects in colonization and persistence in chicken intestine, but did not show significant differences in adhesion, phagocytosis and intracellular survival in murine macrophages. Together, our findings suggest that the capsular heptose modification pathway contributes to bacterial resistance against gastrointestinal host defenses and supports bacterial persistence via its role in serum resistance and invasion of intestinal cells. Our data further suggest a dynamic regulation of expression of this pathway in the gastrointestinal tract.
authors.affiliation: Department of Microbiology and Immunology, Western University, DSB 3031, London, ON, N6A 5C1, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Microbiology and Immunology, Western University, DSB 3031, London, ON, N6A 5C1, Canada.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lange
authors.affiliation: INRS-Institut Armand Frappier, Laval, QC, Canada.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Houle
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Arbatsky
authors.affiliation: Department of Microbiology and Immunology, Western University, DSB 3031, London, ON, N6A 5C1, Canada.|Centre for Infection and Immunity, Queen's University of Belfast, Belfast, UK.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valvano
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Knirel
authors.affiliation: INRS-Institut Armand Frappier, Laval, QC, Canada.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Dozois
authors.affiliation: Department of Microbiology and Immunology, Western University, DSB 3031, London, ON, N6A 5C1, Canada.
authors.forename: Carole
authors.initials: C
authors.lastname: Creuzenet
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D018938:Caco-2 Cells; D002169:Campylobacter Infections / Q000382:microbiology; D016123:Campylobacter jejuni / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000378:metabolism; D002240:Carbohydrate Sequence; D002645:Chickens; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology; D055786:Gene Knockout Techniques; D006539:Heptoses / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007658:Ketone Oxidoreductases / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D014774:Virulence
chemical_list: D001647:Bile Acids and Salts; D029968:Escherichia coli Proteins; D006539:Heptoses; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D011135:Polysaccharides, Bacterial; C110682:wcaG protein, E coli; C068104:kpsM protein, E coli; D007658:Ketone Oxidoreductases; D002238:Carbohydrate Epimerases