Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery
Open accessAbstract
The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β 1 receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites. Hp accomplishes this by secreting another bacterial protein, the serine protease HtrA, which opens cell-to-cell junctions through cleaving epithelial junctional proteins including occludin, claudin-8, and E-cadherin. Using a genetic system expressing a peptide inhibitor, we demonstrate that HtrA activity is necessary for paracellular transmigration of Hp across polarized cell monolayers to reach basolateral membranes and inject CagA. The contribution of this unique signaling cascade to Hp pathogenesis is discussed.
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The zinc-protease PqqE and the serine-protease HtrA disrupt gastric mucosal integrity and thereby facilitate bacterial invasion.
“the zinc-protease PqqE and the serine-protease HtrA disrupt gastric mucosal integrity61–63 and thereby facilitate bacterial invasion.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [62]
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 [62]
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References 48 · Cited by 156
- Authors
- Tegtmeyer, N., Wessler, S., Necchi, V., Rohde, M., Harrer, A., Rau, T. T., Asche, C. I., Boehm, M., Loessner, H., Figueiredo, C., Naumann, M., Palmisano, R., Solcia, E., Ricci, V., & Backert, S.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Salzburg (AT)
- University of Pavia (IT)
- Helmholtz Centre for Infection Research (DE)
- University of Bern (CH)
- Paul Ehrlich Institut (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Corresponding author
- Backert, Steffen
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 22
- Issue
- 4
- Pages
- 552-560.e5
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2763975966
- Cited by
- 156
- References
- 48
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 16 · 2023: 12 · 2022: 13 · 2021: 23 · 2020: 25 · 2019: 28 · 2018: 12 · 2017: 6
- FWCI
- 19.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- German Science Foundation (CRC-1181, TE776/3-1)
- Austrian Science Fund (P-24074)
- Fondazione Cariplo (2009-2532, 2011-0485)
- North Portugal Regional Operational Programme (NORTE-01-0145-FEDER-000029)
- Topics
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Helicobacter pylori, type IV secretion system, basolateral secretion, HtrA serine protease, cell junctions, occludin, claudin-8, E-cadherin, bacterial virulence
- MeSH terms
- Type IV Secretion Systems, High-Temperature Requirement A Serine Peptidase 1, Antigens, Bacterial, Bacterial Proteins, Epithelial Cells, Humans, Fimbriae, Bacterial, Signal Transduction, Helicobacter pylori, Helicobacter Infections, Cell Polarity, Cell Line, Tumor, Transendothelial and Transepithelial Migration
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