Abstract
The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment.
Highlights
Campylobacter infections are associated with 400 million human cases of gastroenteritis worldwide and Campylobacter jejuni is a major cause of bacterial food borne disease and a major causative agent of traveler’s diarrhea (Friedman et al, 2000; Walker, 2005)
Campylobacter jejuni will be exposed to Reactive oxygen species (ROS) during colonization or infection of a host, during survival in the environment and during the course of normal bacterial metabolism
The re-annotation of the C. jejuni NCTC11168 genome sequence (Gundogdu et al, 2007) identified both RrpA and RrpB as putative MarR-type transcriptional regulators and RrpB was previously shown to be involved in the C. jejuni oxidative and aerobic (O2) stress responses (Gundogdu et al, 2011)
Summary
Campylobacter infections are associated with 400 million human cases of gastroenteritis worldwide and Campylobacter jejuni is a major cause of bacterial food borne disease and a major causative agent of traveler’s diarrhea (Friedman et al, 2000; Walker, 2005). C. jejuni is microaerophilic, Campylobacter jejuni RrpA and RrpB growing optimally in an atmosphere of around 10% CO2 and 5% O2 at a temperature between 37 and 42°C (Park, 2002; Garenaux et al, 2008) Despite these microaerophilic growth requirements, C. jejuni can survive in the ambient environment, which may partly explain the bacteria’s success as a highly prevalent pathogen. Under these less unfavorable conditions C. jejuni must have evolved specific adaptation mechanisms (Fields and Thompson, 2008; Olson et al, 2008). The ability to neutralize ROS is essential for C. jejuni survival under optimal conditions, in the ambient environment and within a host where the organism will encounter ROS produced by the host immune system (Imlay, 2008; Atack and Kelly, 2009)
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