Journal article
The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni
mBio, Vol.7(6), 01691
11/15/2016
DOI: 10.1128/mBio.01691-16
PMCID: PMC5111405
PMID: 27935836
Abstract
Campylobacter jejuni is a leading cause of bacterially derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work identified a PAS domain-containing regulator, termed HeuR, as being required for chicken colonization. Here we confirm that both the heme uptake system and HeuR are required for full chicken gastrointestinal tract colonization, with the heuR mutant being particularly affected during competition with wild-type C. jejuni. Transcriptomic analysis identified the chu genes- and those encoding other iron uptake systems-as regulatory targets of HeuR. Purified HeuR bound the chuZA promoter region in electrophoretic mobility shift assays. Consistent with a role for HeuR in chu expression, heuR mutants were unable to efficiently use heme as a source of iron under iron-limiting conditions, and mutants exhibited decreased levels of cell-associated iron by mass spectrometry. Finally, we demonstrate that an heuR mutant of C. jejuni is resistant to hydrogen peroxide and that this resistance correlates to elevated levels of catalase activity. These results indicate that HeuR directly and positively regulates iron acquisition from heme and negatively impacts catalase activity by an as yet unidentified mechanism in C. jejuni.
IMPORTANCE Annually, Campylobacter jejuni causes millions of gastrointestinal infections in the United States, due primarily to its ability to reside within the gastrointestinal tracts of poultry, where it can be released during processing and contaminate meat. In the developing world, humans are often infected by consuming contaminated water or by direct contact with livestock. Following consumption of contaminated food or water, humans develop disease that is characterized by mild to severe diarrhea. There is a need to understand both colonization of chickens, to make food safer, and colonization of humans, to better understand disease. Here we demonstrate that to efficiently colonize a host, C. jejuni requires iron from heme, which is regulated by the protein HeuR. Understanding how HeuR functions, we can develop ways to inhibit its function and reduce iron acquisition during colonization, potentially reducing C. jejuni in the avian host, which would make food safer, or limiting human colonization.
Details
- Title: Subtitle
- The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni
- Creators
- Jeremiah G. Johnson - Michigan State UniversityJennifer A. Gaddy - VA Tennessee Valley Healthcare SystemVictor J. Dirita - Michigan State University
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.7(6), 01691
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/mBio.01691-16
- PMID
- 27935836
- PMCID
- PMC5111405
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Number of pages
- 11
- Grant note
- 2013-67012-25269 / USDA \ National Institute of Food and Agriculture (NIFA) CDA-21K2BX001701 / Veterans Affairs; US Department of Veterans Affairs R21AI111192 / HHS \ National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/15/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696722202771
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