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Published on: February 7, 2018
PerR controls peroxide- and iron-responsive expression of oxidative stress defense genes in Helicobacter hepaticus
Abstract:
Chronic intestinal and hepatic colonization with the microaerophilic murine pathogen Helicobacter hepaticus can lead to a range of inflammatory diseases of the lower digestive tract. Colonization is associated with an active cellular immune response and production of oxygen radicals. During colonization, H. hepaticus needs to cope with and respond to oxidative stress, and here we report on the role of the H. hepaticus PerR-regulator (HH0942) in the expression of the peroxidase-encoding katA (HH0043) and ahpC (HH1564) genes. Transcription of katA and ahpC was induced by hydrogen peroxide, and by iron restriction of growth media. This iron- and hydrogen peroxide-responsive regulation of katA and ahpC was mediated at the transcriptional level, from promoters directly upstream of the genes. Inactivation of the perR gene resulted in constitutive, iron-independent high-level expression of the katA and ahpC transcripts and corresponding proteins. Finally, inactivation of the katA gene resulted in increased sensitivity of H. hepaticus to hydrogen peroxide and reduced aerotolerance. In H. hepaticus, iron metabolism and oxidative stress defense are intimately connected via the PerR regulatory protein. This regulatory pattern resembles that observed in the enteric pathogen Campylobacter jejuni, but contrasts with the pattern observed in the closely related human gastric pathogen Helicobacter pylori.
Insights
Helicobacter hepaticus uses the PerR regulator to control genes involved in oxidative stress defense, like katA and ahpC. This regulation is crucial for the bacteria
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Oxidative Stress Response
Background:
- Chronic Helicobacter hepaticus colonization causes inflammatory diseases.
- H. hepaticus encounters oxidative stress during colonization.
- The PerR regulator's role in oxidative stress response is unknown.
Purpose of the Study:
- Investigate the role of H. hepaticus PerR (HH0942) in regulating oxidative stress genes.
- Determine the impact of PerR on katA (HH0043) and ahpC (HH1564) gene expression.
- Understand the connection between iron metabolism and oxidative stress defense in H. hepaticus.
Main Methods:
- Gene expression analysis (transcription and protein levels).
- Hydrogen peroxide and iron restriction induction assays.
- Gene inactivation studies (perR and katA mutants).
Main Results:
- PerR regulates katA and ahpC expression, which are induced by hydrogen peroxide and iron restriction.
- PerR inactivation leads to constitutive, iron-independent expression of katA and ahpC.
- katA inactivation increases H. hepaticus sensitivity to hydrogen peroxide and reduces aerotolerance.
Conclusions:
- The PerR regulatory protein connects iron metabolism and oxidative stress defense in H. hepaticus.
- This regulatory mechanism is similar to Campylobacter jejuni but differs from Helicobacter pylori.
- PerR-mediated regulation is essential for H. hepaticus survival under oxidative stress conditions.
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