{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:59:28Z","timestamp":1756191568641,"version":"3.41.2"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["16K18928"],"award-info":[{"award-number":["16K18928"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["19K07074"],"award-info":[{"award-number":["19K07074"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["22K15465"],"award-info":[{"award-number":["22K15465"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"GSK | GlaxoSmithKline Japan","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP20fk0108148"],"award-info":[{"award-number":["JP20fk0108148"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP23fk0108678"],"award-info":[{"award-number":["JP23fk0108678"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2023,12,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Helicobacter cinaedi<\/jats:italic>\n            infects the human gut and causes invasive infections such as bacteremia and cellulitis through bacterial translocation. However, the mechanism by which\n            <jats:italic>H. cinaedi<\/jats:italic>\n            attaches to host cells and establishes infection remains unclear. This study aimed to investigate the relationship between a novel putative autotransporter protein,\n            <jats:italic>H. cinaedi<\/jats:italic>\n            autotransporter protein A (HcaA), and its role in pathogenicity. The cytotoxicity of\n            <jats:italic>H. cinaedi<\/jats:italic>\n            infection in colon epithelial cell lines (Caco-2 and HT29) was assessed using a lactate dehydrogenase assay, and it was found that cytotoxicity significantly decreased upon HcaA knockout. Adhesion assays further revealed that the HcaA-knockout strain showed significantly reduced attachment to the human epithelial colorectal adenocarcinoma (Caco-2) cell line compared to that of the wild-type strain. Moreover, the recombinant HcaA protein demonstrated strong adhesion properties to the human monocytic cell line (U937). The adhesive activity was diminished when the Arg-Gly-Asp (RGD) motif in HcaA was replaced with RAD, indicating that the RGD motif in HcaA is crucial for host cell adhesion. To determine the role of HcaA in\n            <jats:italic>H. cinaedi<\/jats:italic>\n            infection\n            <jats:italic>in vivo<\/jats:italic>\n            , C57BL\/6 mice were orally infected with wild-type and HcaA-knockout\n            <jats:italic>H. cinaedi<\/jats:italic>\n            strains. Bacterial colonization was assessed 7, 14, and 28 days post-infection. At 7 days post-infection, colonization was significantly lower in mice infected with the HcaA-knockout strain compared to those infected with the wild-type strain. In conclusion, our findings suggest that HcaA, a novel putative autotransporter protein in\n            <jats:italic>H. cinaedi<\/jats:italic>\n            , plays a significant role as an adhesin in establishing colonization.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Helicobacter<\/jats:italic>\n              species are classified as gastric or enterohepatic according to their habitat. Among enterohepatic\n              <jats:italic>Helicobacter<\/jats:italic>\n              species, which inhabit the intestine, colon, and liver,\n              <jats:italic>Helicobacter cinaedi<\/jats:italic>\n              has been most frequently isolated from humans.\n              <jats:italic>H. cinaedi<\/jats:italic>\n              often causes bacteremia and cellulitis in immunocompromised hosts. Here, we focused on the\n              <jats:italic>H. cinaedi<\/jats:italic>\n              autotransporter protein A (HcaA), a novel virulence factor in\n              <jats:italic>H. cinaedi<\/jats:italic>\n              . We discovered that HcaA contributes to cell adhesion via its Arg-Gly-Asp motif. Furthermore, in animal experiments, bacterial colonization was reduced in mice infected with HcaA-knockout strains, supporting the hypothesis that HcaA contributes to\n              <jats:italic>H. cinaedi<\/jats:italic>\n              adhesion to host cells. Our study provides a novel mechanism for the establishment of\n              <jats:italic>H. cinaedi<\/jats:italic>\n              infections and provides new insights into the role of autotransporter proteins in the establishment of\n              <jats:italic>Helicobacter<\/jats:italic>\n              infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00403-23","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T14:05:00Z","timestamp":1701093900000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of HcaA, a novel autotransporter protein in\n            <i>Helicobacter cinaedi<\/i>\n            , and its role in host cell adhesion"],"prefix":"10.1128","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-1887","authenticated-orcid":false,"given":"Sae","family":"Aoki","sequence":"first","affiliation":[{"name":"Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigetarou","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keigo","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3198-4263","authenticated-orcid":false,"given":"Tsuyoshi","family":"Kenri","sequence":"additional","affiliation":[{"name":"Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8847-1840","authenticated-orcid":false,"given":"Emiko","family":"Rimbara","sequence":"additional","affiliation":[{"name":"Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, 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