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

dc.contributor.authorHarrer, Aileen
dc.contributor.authorBoehm, Manja
dc.contributor.authorBackert, Steffen
dc.contributor.authorTegtmeyer, Nicole
dc.date.accessioned2017-08-17
dc.date.available2017-08-09
dc.date.created2017
dc.date.issued2017-08-17
dc.description.abstractBackground 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 Helicobacter pylori 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. Results 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 ΔhtrA knockout mutants, suggesting that htrA may represent an essential gene in H. pylori. To circumvent this major handicap and to investigate the role of HtrA further, we overexpressed HtrA by introducing a second functional htrA gene copy in the chromosome and studied various virulence properties of the bacteria. The resulting data demonstrate that overexpression of HtrA in H. pylori 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. Conclusions These data provide for the first time genetic evidence in H. pylori that HtrA is a novel major virulence factor controlling multiple pathogenic activities of this important microbe.en
dc.identifier.citationGut Pathogens 9 (2017). <https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-017-0189-6>
dc.identifier.doihttps://doi.org/10.1186/s13099-017-0189-6
dc.identifier.opus-id8701
dc.identifier.urihttps://open.fau.de/handle/openfau/8701
dc.identifier.urnurn:nbn:de:bvb:29-opus4-87010
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/de/deed.de
dc.subjectAdherens junction
dc.subjectTight junction
dc.subjectE-cadherin
dc.subjectHelicobacter pylori
dc.subjectProtease
dc.subjectHtrA
dc.subjectType IV secretion system
dc.subjectT4SS
dc.subjectCagA
dc.subjectEPIYA
dc.subjectSrc
dc.subjectAbl
dc.subjectIntegrin
dc.subjectTranswell
dc.subject.ddcDDC Classification::5 Naturwissenschaften und Mathematik :: 57 Biowissenschaften; Biologie :: 570 Biowissenschaften; Biologie
dc.titleOverexpression of serine protease HtrA enhances disruption of adherens junctions, paracellular transmigration and type IV secretion of CagA by Helicobacter pylorien
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleGut Pathogens
local.journal.volume9
local.sendToDnbfree*
local.subject.fakultaetNaturwissenschaftliche Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2017
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