The HtrA Protease of Campylobacter jejuni Is Required for Heat and Oxygen Tolerance and for Optimal Interaction with Human Epithelial Cells
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Campylobacter jejuni is a predominant cause of food-borne bacterial gastroenteritis in the developed world. We have investigated the importance of a homologue of the periplasmic HtrA protease in C. jejuni stress tolerance. A C. jejuni htrA mutant was constructed and compared to the parental strain, and we found that growth of the mutant was severely impaired both at 44°C and in the presence of the tRNA analogue puromycin. Under both conditions, the level of misfolded protein is known to increase, and we propose that the heat-sensitive phenotype of the htrA mutant is caused by an accumulation of misfolded protein in the periplasm. Interestingly, we observed that the level of the molecular chaperones DnaK and ClpB was increased in the htrA mutant, suggesting that accumulation of nonnative proteins in the periplasm induces the expression of cytoplasmic chaperones. While lack of HtrA reduces the oxygen tolerance of C. jejuni , the htrA mutant was not sensitive to compounds that increase the formation of oxygen radicals, such as paraquat, cumene hydroperoxide, and H 2 O 2 . Using tissue cultures of human epithelial cells (INT407), we found that the htrA mutant adhered to and invaded human epithelial cells with a decreased frequency compared to the wild-type strain. This defect may be a consequence of the observed altered morphology of the htrA mutant. Thus, our results suggest that in C. jejuni , HtrA is important for growth during stressful conditions and has an impact on virulence.
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H. pylori, Salmonella typhimurium and Campylobacter jejuni interact with the host cell epithelium and establish infection by HtrA.
“As H. pylori, Salmonella typhimurium and Campylobacter jejuni, a bacterium responsible for foodborne infections, interact with the host cell epithelium and establish infection by HtrA.79–81”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [80]
Tight junctions are targets of infectious agents such as Pseudomonas aeruginosa (through LasB), H. pylori (PqqE and HtrA), C. jejuni (HtrA), V. cholerae (vibrolysin), Shigella, Salmonella or pathogenic Escherichia coli (SepA).
“Tight junctions are also targets of infectious agents such as Pseudomonas aeruginosa (through LasB),132 H. pylori (PqqE and HtrA),61–63 C. jejuni (HtrA), 79,80 V. cholerae (vibrolysin),10,83 Shigella, Salmonella or pathogenic Escherichia coli (SepA).72,133”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [80]
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Bacterial Proteases and Virulence
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Self-citationThe emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
- Authors
- Brøndsted, L., Andersen, M. T., Parker, M., Jørgensen, K., & Ingmer, H.
- Affiliations
- Department of Veterinary Pathobiology, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark
- Quadram Institute (GB)
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2005-06
- Volume
- 71
- Issue
- 6
- Pages
- 3205-3212
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC1151804
- OpenAlex
- W2134789135
- Cited by
- 98
- References
- 61
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 11 · 2013: 4 · 2012: 4
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Campylobacter jejuni, HtrA protease, heat tolerance, oxygen tolerance, puromycin resistance, protein misfolding, molecular chaperones, DnaK, ClpB, bacterial virulence, epithelial cell invasion, bacterial adhesion, bacterial morphology, stress tolerance
- MeSH terms
- Amino Acid Sequence, Bacterial Adhesion, Cell Line, DNA, Bacterial, Epithelial Cells, Hot Temperature, Heat-Shock Proteins, Humans, Intestines, Mutation, Oxygen, Puromycin, Serine Endopeptidases, Campylobacter jejuni, Heat-Shock Response, Periplasmic Proteins
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