The food-borne pathogen Campylobacter jejuni depends on the AddAB DNA repair system to defend against bile in the intestinal environment

Christopher R Gourley,Michael E Konkel,Nicholas M Negretti

doi:10.1038/s41598-017-14646-9

Christopher R Gourley, Michael E Konkel + Show 1 more

Open Access

https://doi.org/10.1038/s41598-017-14646-9

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Journal: Scientific Reports	Publication Date: Oct 31, 2017
Citations: 19	License type: open-access

Affiliation: Washington State University

Abstract

Accurate repair of DNA damage is crucial to ensure genome stability and cell survival of all organisms. Bile functions as a defensive barrier against intestinal colonization by pathogenic microbes. Campylobacter jejuni, a leading bacterial cause of foodborne illness, possess strategies to mitigate the toxic components of bile. We recently found that growth of C. jejuni in medium with deoxycholate, a component of bile, caused DNA damage consistent with the exposure to reactive oxygen species. We hypothesized that C. jejuni must repair DNA damage caused by reactive oxygen species to restore chromosomal integrity. Our efforts focused on determining the importance of the putative AddAB DNA repair proteins. A C. jejuni addAB mutant demonstrated enhanced sensitivity to deoxycholate and was impaired in DNA double strand break repair. Complementation of the addAB mutant restored resistance to deoxycholate, as well as function of the DNA double strand break repair system. The importance of these findings translated to the natural host, where the AddAB system was found to be required for efficient C. jejuni colonization of the chicken intestine. This research provides new insight into the molecular mechanism utilized by C. jejuni, and possibly other intestinal pathogens, to survive in the presence of bile.

Highlights

Bile plays a critical role in the intestines of both humans and animals as a defensive barrier against colonization by pathogenic microbes
We found that the continuous growth of C. jejuni in medium with a physiological concentration of the bile salt deoxycholate induces the production of reactive oxygen species (ROS), which in turn, causes DNA damage[13]
While RecA has been identified in C. jejuni, its partners in DNA homologous recombination have not been identified, and we suspected that the proteins encoded by the CJH_07760 and CJH_07765 genes are homologs of the AddA and AddB proteins demonstrated to work with RecA in other bacteria

Summary

Introduction

Bile plays a critical role in the intestines of both humans and animals as a defensive barrier against colonization by pathogenic microbes. We found that the continuous growth of C. jejuni in medium with a physiological concentration of the bile salt deoxycholate induces the production of reactive oxygen species (ROS), which in turn, causes DNA damage (double strand breaks)[13]. Based on these findings, we hypothesized that C. jejuni must repair the ROS-induced DNA damage to promote survival. This work revealed that the Campylobacter AddAB proteins contribute to DNA double strand break repair and are necessary for efficient colonization of chickens (the natural host)

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