Campylobacter jejuni Serine Protease HtrA Induces Paracellular Transmigration of Microbiota across Polarized Intestinal Epithelial Cells
Open accessAbstract
Campylobacter jejuni represents an eminent zoonotic germ responsible for foodborne infections causing campylobacteriosis. In addition, infections with C. jejuni constitute a risk factor for the occurrence of inflammatory bowel disease (IBD). In the latter case, patients show inflammatory reactions not only against C. jejuni, but also against the non-infectious microbiota. However, the involved mechanisms and molecular basis are still largely unclear. We recently reported that C. jejuni breaches the intestinal epithelial barrier by secretion of serine protease HtrA (high temperature requirement A), which cleaves several major tight and adherens junction proteins. In the present study, we aimed to study if HtrA-expressing C. jejuni may also trigger the transepithelial migration of non-pathogenic gastrointestinal microbiota. Using confocal immunofluorescence and scanning electron microscopy, we demonstrate that C. jejuni wild-type (wt) as well as the isogenic ∆htrA mutant bind to the surface of polarized intestinal Caco-2 epithelial cells, but do not invade them at the apical side. Instead, C. jejuni wt, but not ∆htrA mutant, disrupt the cellular junctions and transmigrate using the paracellular route between neighboring cells. Using transwell filter systems, we then co-incubated the cells with C. jejuni and non-invasive microbiota strains, either Escherichia coli or Lactococcus lactis. Interestingly, C. jejuni wt, but not ∆htrA mutant, induced the efficient transmigration of these microbiota bacteria into the basal compartment. Thus, infection of the intestinal epithelium with C. jejuni causes local opening of cellular junctions and paracellular translocation in an HtrA-dependent manner, which paves the way for transmigration of microbiota that is otherwise non-invasive. Taken together, these findings may have impacts on various Campylobacter-associated diseases such as IBD, which are discussed here.
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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 [79]
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 [79]
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- Authors
- Sharafutdinov, I., Tegtmeyer, N., Müsken, M., & Backert, S.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Helmholtz Centre for Infection Research (DE)
- Corresponding author
- Backert, Steffen
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2022-03-30
- Volume
- 12
- Issue
- 4
- Pages
- 521
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC9027135
- OpenAlex
- W4220740533
- Cited by
- 23
- References
- 46
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 2
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- OPUS Repository (Kooperativer Bibliotheksverbund Berlin-Brandenburg) (submittedVersion, cc-by)
- Funders
- Federal Ministry of Education and Research (IP9/ 01KI2007E)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Campylobacter jejuni, HtrA serine protease, gut microbiota, intestinal epithelial barrier, tight junctions, adherens junctions, Caco-2 cells, inflammatory bowel disease, Escherichia coli, Lactococcus lactis, bacterial invasion
- MeSH terms
- Humans, Serine Endopeptidases, Inflammatory Bowel Diseases, Campylobacter jejuni, Caco-2 Cells, Serine Proteases, Microbiota
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