EptC of campylobacter jejuni mediates phenotypes involved in host interactions and virulence

Thomas W. Cullen, John P. O'Brien, David R. Hendrixson, David K. Giles, Rhonda I. Hobb, Stuart A. Thompson, Jennifer S. Brodbelt, M. Stephen Trent

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Campylobacter jejuni is a natural commensal of the avian intestinal tract. However, the bacterium is also the leading cause of acute bacterial diarrhea worldwide and is implicated in development of Guillain-Barré syndrome. Like many bacterial pathogens, C. jejuni assembles complex surface structures that interface with the surrounding environment and are involved in pathogenesis. Recent work in C. jejuni identified a gene encoding a novel phosphoethanolamine (pEtN) transferase, EptC (Cj0256), that plays a promiscuous role in modifying the flagellar rod protein, FlgG; the lipid A domain of lipooligosaccharide (LOS); and several N-linked glycans. In this work, we report that EptC catalyzes the addition of pEtN to the first heptose sugar of the inner core oligosaccharide of LOS, a fourth enzymatic target. We also examine the role pEtN modification plays in circumventing detection and/or killing by host defenses. Specifically, we show that modification of C. jejuni lipid A with pEtN results in increased recognition by the human Toll-like receptor 4-myeloid differentiation factor 2 (hTLR4-MD2) complex, along with providing resistance to relevant mammalian and avian antimicrobial peptides (i.e., defensins). We also confirm the inability of aberrant forms of LOS to activate Toll-like receptor 2 (TLR2). Most exciting, we demonstrate that strains lacking eptC show decreased commensal colonization of chick ceca and reduced colonization of BALB/cByJ mice compared to wild-type strains. Our results indicate that modification of surface structures with pEtN by EptC is key to its ability to promote commensalism in an avian host and to survive in the mammalian gastrointestinal environment.

Original languageEnglish (US)
Pages (from-to)430-440
Number of pages11
JournalInfection and Immunity
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Cullen, T. W., O'Brien, J. P., Hendrixson, D. R., Giles, D. K., Hobb, R. I., Thompson, S. A., Brodbelt, J. S., & Trent, M. S. (2013). EptC of campylobacter jejuni mediates phenotypes involved in host interactions and virulence. Infection and Immunity, 81(2), 430-440. https://doi.org/10.1128/IAI.01046-12