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

Publication date: 11 October 2017
Source:Cell Host & Microbe, Volume 22, Issue 4
Author(s): Nicole Tegtmeyer, Silja Wessler, Vittorio Necchi, Manfred Rohde, Aileen Harrer, Tilman T. Rau, Carmen Isabell Asche, Manja Boehm, Holger Loessner, Ceu Figueiredo, Michael Naumann, Ralf Palmisano, Enrico Solcia, Vittorio Ricci, Steffen Backert
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.

Graphical abstract

Teaser

The type IV secretion system of Helicobacter pylori requires basolateral integrin receptors for its function. Tegtmeyer et al. unravel that secreted serine protease HtrA opens cell-to-cell junctions by cleaving occludin, claudin-8, and E-cadherin. This allows bacterial transmigration across polarized epithelial cells to reach integrins for injecting CagA at basolateral membranes.


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