The Campylobacter jejuni Type VI Secretion System Enhances the Oxidative Stress Response and Host Colonization.

Janie Liaw,Abderrahman Hachani,Cadi Davies,Ioan Pet,Filip Sima,Nick Dorrell,Lavinia Stef,Nicolae Corcionivoschi,Abdi Elmi,Brendan W Wren,Ozan Gundogdu,Geunhye Hong,Alexandros Stratakos

doi:10.3389/fmicb.2019.02864

Abstract

The role of the Type VI secretion system (T6SS) in Campylobacter jejuni is poorly understood despite an increasing prevalence of the T6SS in recent C. jejuni isolates in humans and chickens. The T6SS is a contractile secretion machinery capable of delivering effectors that can play a role in host colonization and niche establishment. During host colonization, C. jejuni is exposed to oxidative stress in the host gastrointestinal tract, and in other bacteria the T6SS has been linked with the oxidative stress response. In this study, comparisons of whole genome sequences of a novel human isolate 488 with previously sequenced strains revealed a single highly conserved T6SS cluster shared between strains isolated from humans and chickens. The presence of a functional T6SS in the 488 wild-type strain is indicated by expression of T6SS genes and secretion of the effector TssD. Increased expression of oxidative stress response genes katA, sodB, and ahpC, and increased oxidative stress resistance in 488 wild-type strain suggest T6SS is associated with oxidative stress response. The role of the T6SS in interactions with host cells is explored using in vitro and in vivo models, and the presence of the T6SS is shown to increase C. jejuni cytotoxicity in the Galleria mellonella infection model. In biologically relevant models, the T6SS enhances C. jejuni interactions with and invasion of chicken primary intestinal cells and enhances the ability of C. jejuni to colonize chickens. This study demonstrates that the C. jejuni T6SS provides defense against oxidative stress and enhances host colonization, and highlights the importance of the T6SS during in vivo survival of T6SS-positive C. jejuni strains.

Highlights

Campylobacter jejuni, a Gram-negative microaerophilic bacteria, is the leading cause of bacterial foodborne gastroenteritis worldwide
Comparisons of the 488, 43431, and RC039 genome sequences with previously published sequences for other T6SS-positive C. jejuni strains (Lertpiriyapong et al, 2012; Bleumink-Pluym et al, 2013) revealed a T6SS cluster that is highly conserved, sharing synteny between strains and with other Campylobacter species isolated from humans and chickens (Figure 1)
T6SS plays a role in the ability of C. jejuni to infect chickens, an in vitro model was used to examine the potential of C. jejuni to adhere to and invade chicken primary intestinal cells

Summary

Introduction

Campylobacter jejuni, a Gram-negative microaerophilic bacteria, is the leading cause of bacterial foodborne gastroenteritis worldwide. C. jejuni infection in humans can lead to diarrhea, vomiting, abdominal pain, fever, with symptoms generally appearing 2–5 days following exposure to an infectious dose as low as 500–900 bacteria (Robinson, 1981; Kaakoush et al, 2015). C. jejuni colonizes chickens and other avian species and an estimated 70% of raw chicken sold in supermarkets in the United Kingdom will be contaminated with C. jejuni (Kaakoush et al, 2015). The spread of C. jejuni through chicken flocks in farms can have a vast economic impact on the poultry industry and an increased spread of C. jejuni in chickens can subsequently affect the rates of infection in humans (Newell and Fearnley, 2003; Skarp et al, 2016)

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Results

Conclusion