A mutator phenotype promoting the emergence of spontaneous oxidative stress-resistant mutants in Campylobacter jejuni

Abstract

<p><em>Campylobacter jejuni</em> is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, <em>C. jejuni</em> must be able to defend against oxidative stress encountered both in the host and in the environment. How <em>Campylobacter</em> utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX^R) in <em>C. jejuni</em>. We further demonstrated that MutY malfunction didn't directly contribute to the OX^R phenotype, but increased the spontaneous mutation rate in the peroxide regulator gene <em>perR</em>, which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX^R phenotype and facilitating <em>Campylobacter</em> survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX^R mutants in bacterial organisms.</p>