Type VI secretion system contributes to Enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species (ROS)

PLoS Pathog. 2017 Mar 13;13(3):e1006246. doi: 10.1371/journal.ppat.1006246. eCollection 2017 Mar.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells.

MeSH terms

  • Animals
  • Blotting, Western
  • Catalase / metabolism*
  • Disease Models, Animal
  • Enterohemorrhagic Escherichia coli / metabolism
  • Enterohemorrhagic Escherichia coli / pathogenicity*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Host-Pathogen Interactions / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Type VI Secretion Systems / metabolism*
  • Virulence / physiology

Substances

  • Escherichia coli Proteins
  • Reactive Oxygen Species
  • Type VI Secretion Systems
  • Catalase

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 31270173, No. 81601738 and No. 81361120383), the State Key Development Programs for Basic Research of China (973 Program No. 2015CB554203), Key Research and Development Project of China (No. 2016YFA0500600), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.