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

Baoshan Wan; Qiufen Zhang; Jinjing Ni; Shuxian Li; Donghua Wen; Jun Li; Haihan Xiao; Ping He; Hong-Yu Ou; Jing Tao; Qihui Teng; Jie Lu; Wenjuan Wu; Yu-Feng Yao

doi:10.1371/journal.ppat.1006246

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.

Authors

Baoshan Wan¹, Qiufen Zhang¹, Jinjing Ni¹, Shuxian Li¹, Donghua Wen², Jun Li^{3

4}, Haihan Xiao¹, Ping He¹, Hong-Yu Ou³, Jing Tao¹, Qihui Teng¹, Jie Lu⁵, Wenjuan Wu², Yu-Feng Yao^{1

2}

Affiliations

¹ Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
³ State Key Laboratory for Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
⁴ College of Biological Engineering, Zhejiang University of Technology, Hangzhou, China.
⁵ Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.