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

Tegtmeyer N, Wessler S, Necchi V, Rohde M, Harrer A, Rau T, Asche I, Böhm M, Loessner H, Figueiredo C, Naumann M, Palmisano R, Solcia E, Ricci V, Backert S (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Cell Host & Microbe Elsevier (Cell Press)

Book Volume: 22

Pages Range: 552-560.e5

Journal Issue: 4

DOI: 10.1016/j.chom.2017.09.005

Abstract

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

Authors with CRIS profile

Nicole Tegtmeyer-Backert Lehrstuhl für Mikrobiologie Aileen Harrer Lehrstuhl für Mikrobiologie Isabell Asche Lehrstuhl für Mikrobiologie Manja Böhm Lehrstuhl für Mikrobiologie Ralf Palmisano Optical Imaging Center Erlangen (OICE) Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) DE Germany (DE) Università degli Studi di Pavia IT Italy (IT) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Universidade do Porto PT Portugal (PT) Otto-von-Guericke-Universität Magdeburg DE Germany (DE)

How to cite

APA:

Tegtmeyer, N., Wessler, S., Necchi, V., Rohde, M., Harrer, A., Rau, T.,... Backert, S. (2017). Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery. Cell Host & Microbe, 22(4), 552-560.e5. https://dx.doi.org/10.1016/j.chom.2017.09.005

MLA:

Tegtmeyer, Nicole, et al. "Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery." Cell Host & Microbe 22.4 (2017): 552-560.e5.

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