{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T19:19:35Z","timestamp":1792351175847,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010326","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB914\/Project B5\/DFG HA2697\/16-2"],"award-info":[{"award-number":["SFB914\/Project B5\/DFG HA2697\/16-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB914\/Project Z01"],"award-info":[{"award-number":["SFB914\/Project Z01"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"LMU Munich F\u00f6FoLe Program","award":["Reg.-Nr. 54\/2014"],"award-info":[{"award-number":["Reg.-Nr. 54\/2014"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Helicobacter pylori<\/jats:italic>colonizes half of the global population and causes gastritis, peptic ulcer disease or gastric cancer. In this study, we were interested in human annexin (ANX), which comprises a protein family with diverse and partly unknown physiological functions, but with a potential role in microbial infections and possible involvement in gastric cancer. We demonstrate here for the first time that<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>is able to specifically bind ANXs. Binding studies with purified<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>LPS and specific<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>LPS mutant strains indicated binding of ANXA5 to lipid A, which was dependent on the lipid A phosphorylation status. Remarkably, ANXA5 binding almost completely inhibited LPS-mediated Toll-like receptor 4- (TLR4) signaling in a TLR4-specific reporter cell line. Furthermore, the interaction is relevant for gastric colonization, as a mouse-adapted<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>increased its ANXA5 binding capacity after gastric passage and its ANXA5 incubation<jats:italic>in vitro<\/jats:italic>interfered with TLR4 signaling. Moreover, both ANXA2 and ANXA5 levels were upregulated in<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>-infected human gastric tissue, and<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>can be found in close association with ANXs in the human stomach. Furthermore, an inhibitory effect of ANXA5 binding for CagA translocation could be confirmed. Taken together, our results highlight an adaptive ability of<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>to interact with the host cell factor ANX potentially dampening innate immune recognition.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010326","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T18:47:30Z","timestamp":1645123650000},"page":"e1010326","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling"],"prefix":"10.1371","volume":"18","author":[{"given":"Barbara","family":"Schmidinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Petri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Lettl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8876-5176","authenticated-orcid":true,"given":"Sukumar","family":"Namineni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0307-7022","authenticated-orcid":true,"given":"Hellen","family":"Ishikawa-Ankerhold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-5019","authenticated-orcid":true,"given":"Luisa Fernanda","family":"Jim\u00e9nez-Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-0947","authenticated-orcid":true,"given":"Rainer","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"issue":"15","key":"ppat.1010326.ref001","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1056\/NEJMra020542","article-title":"Helicobacter pylori infection","volume":"347","author":"S Suerbaum","year":"2002","journal-title":"N Engl J Med"},{"key":"ppat.1010326.ref002","doi-asserted-by":"crossref","first-page":"10570","DOI":"10.1016\/S0021-9258(19)50054-0","article-title":"Purification and characterization of the vacuolating toxin from Helicobacter pylori","volume":"267","author":"TL Cover","year":"1992","journal-title":"J Biol Chem"},{"key":"ppat.1010326.ref003","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1073\/pnas.90.12.5791","article-title":"Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer","volume":"90","author":"A Covacci","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1010326.ref004","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1126\/science.287.5457.1497","article-title":"Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion","volume":"287","author":"S Odenbreit","year":"2000","journal-title":"Science"},{"issue":"9","key":"ppat.1010326.ref005","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrc1433","article-title":"Oncogenic mechanisms of the Helicobacter pylori CagA protein","volume":"4","author":"M. 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