Role of capsular modified heptose in the virulence of Campylobacter jejuni

Mol Microbiol. 2015 Jun;96(6):1136-58. doi: 10.1111/mmi.12995. Epub 2015 Apr 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Capsules / genetics
  • Bacterial Capsules / metabolism*
  • Bile Acids and Salts / metabolism
  • Caco-2 Cells
  • Campylobacter Infections / microbiology
  • Campylobacter jejuni / enzymology
  • Campylobacter jejuni / genetics
  • Campylobacter jejuni / metabolism
  • Campylobacter jejuni / pathogenicity*
  • Carbohydrate Epimerases / genetics
  • Carbohydrate Epimerases / metabolism
  • Carbohydrate Sequence
  • Chickens
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gastrointestinal Tract / microbiology
  • Gene Knockout Techniques
  • Heptoses / genetics
  • Heptoses / metabolism*
  • Humans
  • Ketone Oxidoreductases / genetics
  • Ketone Oxidoreductases / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Polysaccharides, Bacterial / metabolism*
  • RAW 264.7 Cells
  • Virulence

Substances

  • Bile Acids and Salts
  • Escherichia coli Proteins
  • Heptoses
  • Membrane Transport Proteins
  • Multienzyme Complexes
  • Polysaccharides, Bacterial
  • wcaG protein, E coli
  • kpsM protein, E coli
  • Ketone Oxidoreductases
  • Carbohydrate Epimerases