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

Ozan Gundogdu,Abdi Elmi,Brendan W. Wren,Nick Dorrell,Daiani T. da Silva,Banaz Mohammad,Arnoud H. M. van Vliet

doi:10.3389/fmicb.2016.02117

Ozan Gundogdu, Abdi Elmi + Show 5 more

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https://doi.org/10.3389/fmicb.2016.02117

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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.

Highlights

Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide with an estimated 400 million human infections occurring each year (Ruiz-Palacios, 2007)
To assess the distribution of rrpA and rrpB in C. jejuni and C. coli we utilized a collection of 4,232 Campylobacter genome sequences (3,746 C. jejuni and 486 C. coli) from public databases (Cody et al, 2013; Brown et al, 2015), which were phylogenetically clustered using FFPry feature frequency profiling (Van Vliet and Kusters, 2015; Dwivedi et al, 2016) and further analyzed for multilocus sequence typing (MLST) sequence type and clonal complex (Pearson et al, 2015)
C. jejuni contains a number of different mechanisms for counteracting the effects of oxidative stress and the control of the C. jejuni oxidative stress response is complex involving multiple inter-linked levels of regulation (Atack and Kelly, 2009)

Summary

Introduction

Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide with an estimated 400 million human infections occurring each year (Ruiz-Palacios, 2007). The predominance of C. jejuni can be attributed to the ability to survive in the environment as well as within avian and mammalian hosts despite the microaerophilic nature of this bacterium. C. jejuni has evolved specific adaptation mechanisms to survive under atmospheric oxygen conditions (Kim et al, 2015). In addition to aerobic stress such as the exposure to increased levels of oxygen under atmospheric conditions, C. jejuni can encounter stress conditions within the host, oxidative stress in the form of reactive oxygen species (ROS) during in vivo survival (Fang, 2004; Palyada et al, 2009). The accumulation of ROS in the bacterial cytoplasm and periplasm leads to damage of nucleic acids, proteins and membrane structures (Atack and Kelly, 2009)

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