Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery.

Tegtmeyer, Nicole; Wessler, Silja; Necchi, Vittorio; Rohde, Manfred; Harrer, Aileen; Rau, Tilman; Asche, Carmen Isabell; Boehm, Manja; Loessner, Holger; Figueiredo, Ceu; Naumann, Michael; Palmisano, Ralf; Solcia, Enrico; Ricci, Vittorio; Backert, Steffen (2017). Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery. Cell host & microbe, 22(4), 552-560.e5. Cell Press 10.1016/j.chom.2017.09.005

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The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β1 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Rau, Tilman

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1931-3128

Publisher:

Cell Press

Language:

English

Submitter:

Tilman Rau

Date Deposited:

14 Dec 2017 10:13

Last Modified:

24 Oct 2019 20:08

Publisher DOI:

10.1016/j.chom.2017.09.005

PubMed ID:

29024645

Uncontrolled Keywords:

CagA E-cadherin Helicobacter HtrA T4SS claudin integrin occludin protease serine protease

BORIS DOI:

10.7892/boris.107520

URI:

https://boris.unibe.ch/id/eprint/107520

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