Overexpression of serine protease HtrA enhances disruption of adherens junctions, paracellular transmigration and type IV secretion of CagA by Helicobacter pylori

• Published in: Gut pathogens Vol. 9; no. 1; p. 40
• Main Authors: Harrer, Aileen, Boehm, Manja, Backert, Steffen, Tegtmeyer, Nicole
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.07.2017; BioMed Central; BMC
• Subjects: Adherens junction; Adherens junctions; Apoptosis; Bacteria; Cadherins; Cell adhesion & migration; Cell junctions; E-cadherin; Epithelial cells; Gene expression; Genetic aspects; Helicobacter pylori; HtrA; HtrA gene; Interleukin 8; Junctional complexes (Epithelium); Kinases; Pathogens; Phosphorylation; Physiological aspects; Protease; Proteases; Proteins; Quality control; Rodents; Serine; Serine proteinase; Tight junction; Tumor suppressor genes; Virulence factors; Src; T4SS; CagA; Abl; E-cadherin; Transwell; Adherens junction; Integrin; Helicobacter pylori; Protease; EPIYA; HtrA; Tight junction; Type IV secretion system
• ISSN: 1757-4749; 1757-4749
• DOI: 10.1186/s13099-017-0189-6

The serine protease HtrA is an important factor for regulating stress responses and protein quality control in bacteria. In recent studies, we have demonstrated that the gastric pathogen can secrete HtrA into the extracellular environment, where it cleaves-off the ectodomain of the tumor suppressor and adherens junction protein E-cadherin on gastric epithelial cells. E-cadherin cleavage opens cell-to-cell junctions, allowing paracellular transmigration of the bacteria across polarized monolayers of MKN-28 and Caco-2 epithelial cells. However, rapid research progress on HtrA function is mainly hampered by the lack of Δ knockout mutants, suggesting that may represent an essential gene in . To circumvent this major handicap and to investigate the role of HtrA further, we overexpressed HtrA by introducing a second functional gene copy in the chromosome and studied various virulence properties of the bacteria. The resulting data demonstrate that overexpression of HtrA in gives rise to elevated rates of HtrA secretion, cleavage of E-cadherin, bacterial transmigration and delivery of the type IV secretion system (T4SS) effector protein CagA into polarized epithelial cells, but did not affect IL-8 chemokine production or the secretion of vacuolating cytotoxin VacA and γ-glutamyl-transpeptidase GGT. These data provide for the first time genetic evidence in that HtrA is a novel major virulence factor controlling multiple pathogenic activities of this important microbe.