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

Beitrag in einer Fachzeitschrift

Details zur Publikation

Autor(en): Tegtmeyer N, Wessler S, Necchi V, Rohde M, Harrer A, Rau T, Asche CI, Böhm M, Loessner H, Figueiredo C, Naumann M, Palmisano R, Solcia E, Ricci V, Backert S
Zeitschrift: Cell Host & Microbe
Jahr der Veröffentlichung: 2017
Band: 22
Heftnummer: 4
Seitenbereich: 552-560.e5
ISSN: 1931-3128


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.

FAU-Autoren / FAU-Herausgeber

Asche, Carmen Isabell
Lehrstuhl für Mikrobiologie
Backert, Steffen Prof. Dr.
Lehrstuhl für Mikrobiologie
Böhm, Manja Dr.
Lehrstuhl für Mikrobiologie
Harrer, Aileen
Lehrstuhl für Mikrobiologie
Palmisano, Ralf Dr.
Optical Imaging Center Erlangen (OICE)

Autor(en) der externen Einrichtung(en)
Helmholtz-Zentrum für Infektionsforschung (HZI)
Otto-von-Guericke-Universität Magdeburg
Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI)
Universidade do Porto
Università degli Studi di Pavia
Universität Salzburg (Paris Lodron Universität Salzburg)


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

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.


Zuletzt aktualisiert 2019-25-02 um 07:09