PerR controls oxidative stress defence and aerotolerance but not motility-associated phenotypes of Campylobacter jejuni

Handley, Rebecca A.; Mulholland, Francis; Reuter, Mark; Ramachandran, Vinoy K.; Musk, Heather; Clissold, Leah; Brun, Nick E. Le; Vliet, Arnoud H. M. van

doi:10.1099/mic.0.000109

Cited by 26 publications

(34 citation statements)

References 62 publications

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“…Interestingly, C. jejuni, a Gram-negative bacterium, lacks OxyR and instead possesses the metalloregulator PerR, which is normally found in Gram-positive bacteria such as B. subtilis (26), Staphylococcus aureus (27), Enterococcus faecalis (28), and Streptococcus pyogenes (29). Although the insertional inactivation of PerR has been linked to increased aerotolerance and hyperresistance to H 2 O 2 in C. jejuni (10,12,30), spontaneous mutations conferring peroxide resistance in Campylobacter have not been described. In this study, the MutY mutation in the mutator isolate CMT was found to increase the spontaneous mutation frequency in perR, leading to malfunction of PerR, derepression of the PerR regulon, and consequently the increased emergence of OX R mutants in Campylobacter.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies showed that C. jejuni perR mutants displayed significantly increased peroxide resistance and aerotolerance (10,12,30). For example, there were 2 to 3 log more surviving C. jejuni perR insertional mutants than there were wild-type cells after 9 h of incubation under aerobic conditions (30). Recently, aerotolerant C. jejuni and Campylobacter coli have been increasingly isolated from various sources, including chicken or retail meat samples (34-36).…”

Section: Discussionmentioning

confidence: 99%

“…However, elevated mutations in perR may facilitate Campylobacter survival under certain conditions, such as the food production environment, where Campylobacter is exposed to high-level oxidative stress. Multiple studies showed that C. jejuni perR mutants displayed significantly increased peroxide resistance and aerotolerance (10,12,30). For example, there were 2 to 3 log more surviving C. jejuni perR insertional mutants than there were wild-type cells after 9 h of incubation under aerobic conditions (30).…”

Section: Discussionmentioning

confidence: 99%

“…PerR plays an important role in defense against oxidative stress in C. jejuni (3,12,30). PerR represses the expression of katA and ahpC, and insertional mutation of perR results in overexpression of the KatA and AhpC proteins, which makes C. jejuni hyperresistant to peroxide stresses such as cumene hydroperoxide and hydrogen peroxide (10).…”

Section: Discussionmentioning

confidence: 99%

“…In order to investigate the role of the single-nucleotide changes in affecting the binding of PerR to the promoter regions regulated by PerR, EMSAs were performed by a procedure described previously (30,51), with some modifications. Briefly, primers KatAPromF/KatAPromR and DnaEPromF/DnaEPromR (30) were used to amplify the promoter regions of katA and dnaE, respectively.…”

Section: Methodsmentioning

confidence: 99%

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A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni

Dai

Şahin

Tang

et al. 2017

Appl Environ Microbiol

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Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter 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 C. jejuni. 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 perR, 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 Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. ABSTRACT Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter 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 C. jejuni. We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR, 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 Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms.IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, t...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni

Dai

Şahin

Tang

et al. 2017

Appl Environ Microbiol

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Crystal structure of Campylobacter jejuni peroxide regulator

et al. 2018

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In Campylobacter jejuni (Cj), the metal-cofactored peroxide response regulator (PerR) transcription factor allows C. jejuni to respond to oxidative stresses. The crystal structure of the metalated form of CjPerR shows that the protein folds as an asymmetric dimer displaying structural differences in the orientation of its DNA-binding domain. Comparative analysis shows that such asymmetry is a conserved feature among crystallized PerR proteins, and mutational analysis reveals that residues found in the first α-helix of CjPerR contribute to DNA binding. These studies present the structure of CjPerR protein and highlight structural heterogeneity in the orientation of the metalated PerR DNA-binding domain which may underlie the ability of PerR to recognize DNA, control gene expression, and contribute to bacterial pathogenesis.

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Mechanistic concepts involved in biofilm associated processes of Campylobacter jejuni: persistence and inhibition in poultry environments

Bundurus,

Balta,

Pet

et al. 2024

Poultry Science

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PerR controls oxidative stress defence and aerotolerance but not motility-associated phenotypes of Campylobacter jejuni

Cited by 26 publications

References 62 publications

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni

Crystal structure of Campylobacter jejuni peroxide regulator

Mechanistic concepts involved in biofilm associated processes of Campylobacter jejuni: persistence and inhibition in poultry environments

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