Identification of pathogenicity island genes associated with loss of type iv secretion function during murine infection with helicobacter pylori

Lori M. Hansen, Dylan J. Dekalb, Lucy P. Cai, Jay V. Solnick

Research output: Contribution to journalArticle

Abstract

Chronic Helicobacter pylori colonization in animal models often leads to downregulation of the type IV secretion system (T4SS), typically by recombination in cagY, which is an essential T4SS gene. However, 17 other cag pathogenicity island (cagPAI) genes, as well as some non-cagPAI genes, are also essential for T4SS function. To get a more complete picture of how H. pylori regulates the T4SS during animal colonization, we examined cagY in 534 mouse-passaged isolates that lost T4SS function, defined as a normalized interleukin-8 (IL-8) value of <0.3 relative to the input H. pylori strain PMSS1. In order to analyze the genetic changes in the strains with unchanged cagY, we sequenced the entire pathogenicity island of 60 such isolates using single-molecule, real-Time (SMRT) sequencing technology (PacBio, Menlo Park, CA), and we compared the results to the PMSS1 wild type (WT). Of the 534 strains, 271 (51%) showed evidence of recombination in cagY, but we also found indels or nonsynonymous changes in 13 other essential cagPAI genes implicated in H. pylori T4SS function, most commonly cag5, cag10, and cagA. While cagY recombination is the most common mechanism by which H. pylori downregulates T4SS function during murine infection, loss of function is also associated with changes in other essential cagPAI genes.

Original languageEnglish (US)
Article numbere00801
JournalInfection and immunity
Volume88
Issue number6
DOIs
StatePublished - Jun 1 2020

Keywords

  • Helicobacter
  • Mice
  • Pylori
  • Type IV secretion system

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Identification of pathogenicity island genes associated with loss of type iv secretion function during murine infection with helicobacter pylori'. Together they form a unique fingerprint.

  • Cite this