The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance

Abstract

Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide. Despite the microaerophilic nature of the bacterium, C. jejuni can survive the atmospheric oxygen conditions in the environment. Bacteria that can survive either within a host or in the environment like C. jejuni require variable responses to survive the stresses associated with exposure to different levels of reactive oxygen species. The MarR-type transcriptional regulators RrpA and RrpB have recently been shown to play a role in controlling both the C. jejuni oxidative and aerobic stress responses. Analysis of 3,746 C. jejuni and 486 C. coli genome sequences showed that whilst rrpA is present in over 99% of C. jejuni strains, the presence of rrpB is restricted and appears to correlate with specific MLST clonal complexes (predominantly ST-21 and ST-61). C. coli strains in contrast lack both rrpA and rrpB. In C. jejuni rrpB+ strains, the rrpB gene is located within a variable genomic region containing the IF subtype of the type I Restriction-Modification (hsd) system, whilst this variable genomic region in C. jejuni rrpB- strains contains the IAB subtype hsd system and not the rrpB gene. C. jejuni rrpB- strains exhibit greater resistance to peroxide and aerobic stress than C. jejuni rrpB+ strains. Inactivation of rrpA resulted in increased sensitivity to peroxide stress in rrpB+ strains, but not in rrpB- strains. Mutation of rrpA resulted in reduced killing of Galleria mellonella larvae and enhanced biofilm formation independent of rrpB status. The oxidative and aerobic stress responses of rrpB- and rrpB+ strains suggest adaptation of C. jejuni within different hosts and niches that can be linked to specific MLST clonal complexes.

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

“…A MarR family transcriptional regulator TctR was recently shown to regulate the T6SS-2 gene cluster in B. pseudomallei (Losada et al, 2018). Previous studies have also shown that the MarR family transcriptional regulators RrpA and RrpB are important in regulating both oxidative and aerobic stress responses in C. jejuni and therefore play a role in enhancing bacterial survival both in the hosts and in the environment (Gundogdu et al, 2011(Gundogdu et al, , 2015(Gundogdu et al, , 2016. As our results indicate that the C. jejuni T6SS is also associated with the oxidative stress response, it is tempting to speculate that the RrpA and RrpB regulators may in some way be linked to the T6SS.…”

C8J_1298, a bifunctional thiol oxidoreductase of Campylobacter jejuni, affects Dsb (disulfide bond) network functioning

“…Specially, we wondered whether C8J_1298 participates in this process. It should be noticed that due to the differences in the stress regulation mechanisms, C. jejuni 81116 exhibits greater resistance to peroxide stress than strains 11168H and 81-176 [58]. We compared the sensitivity to oxidative stress, induced by H 2 O 2, of wt, Δc8j_1298 (AB1), ΔCjdsbD (AB2) and Δc8j_1298ΔCjdsbD (AB3) mutated strains by determining their survival under oxidative stress conditions.…”

“…To examine susceptibility to oxidative stress, we performed viability assays as previously described [58,90,91]. Briefly, C. jejuni cells were harvested from BHI-SG liquid cultures (16-18 h of incubation under microaerobic conditions) and OD600 nm was adjusted to 0.5.…”

Molecules Autoinducer 2 and cjA and Their Impact on Gene Expression in <b><i>Campylobacter jejuni</i></b>

“…For this reason, C. jejuni encodes a set of important genes which are responsible for aerobic and oxidative stress responses, including katA, ahpC, tpx, bcp, msrAB, and sodB [Atack and Kelly, 2009]. These genes are regulated via a number of regulatory proteins including PerR, Fur, CsrA, CosR, RrpA, and RrpB [Askoura et al, 2016;Fields and Thompson, 2008;Gundogdu et al, 2016]. In addition, the sensor kinase protein CprS is included in the oxidative stress response machinery.…”