Crosstalk between nitrosative and oxidative stress in the enteric pathogen Campylobacter jejuni

Abstract P1

Presenter: Aidan J Taylor (University of Sheffield)

C. jejuni is a microaerophilic enteric pathogen and the leading cause of bacterial gastroenteritis worldwide. During infection, C. jejuni will encounter both nitrosative and oxidative stress generated by the host immune system. Specifically, host neutrophils have high myeloperoxidase activity which generates reactive chlorine species (RCS), namely hypochlorite, reaching local concentrations in the mM range. Some bacteria possess hypochlorite specific regulators which induce a defence response, however no such regulator is evident in C. jejuni. To understand how C. jejuni responds to RCS, RNAseq analysis was performed on C. jejuni after treatment with hypochlorite. Surprisingly, we discovered that the nitric oxide (NO) responsive regulator NssR was activated by hypochlorite. NssR is canonically activated by NO, which is generated in the host by the inducible nitric oxide synthase iNOS, primarily leading to upregulation of the C. jejuni globin cgb, involved in NO detoxification. Here, we demonstrate how NssR responds to both NO and RCS, and discuss the broader implications for crosstalk between nitrosative and oxidative stress.

Presenting in Speaking session 2 - Pathogenesis