{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:44:35Z","timestamp":1777614275211,"version":"3.51.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria meningitidis<\/jats:named-content>NhhA (<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria<\/jats:named-content>hia\/hsf homologue A) is an oligomeric outer membrane protein belonging to the family of trimeric autotransporter adhesins. NhhA mediates the interaction of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>with human epithelial cells and components of the extracellular matrix. The recombinant protein is able to induce bactericidal antibodies and hence has also been considered a potential vaccine candidate. In this study, we analyzed the production of NhhA in a large panel of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>strains belonging to different serogroups and clonal complexes. We found that trimeric NhhA was produced at different levels by the various strains tested. In some strains belonging to the clonal complex ST41\/44, the protein is detectable only as a monomer. Sequencing of the<jats:italic>nhhA<\/jats:italic>gene and generation of complementing strains in different genetic backgrounds have proved that a single mutation (Gly to Asp) in the translocator domain affected both trimerization and surface localization of NhhA.<jats:italic>In vitro<\/jats:italic>infection assays showed that this mutation impairs meningococcal NhhA-mediated adhesion, suggesting that strains carrying the mutation may rely on different strategies or molecules to mediate interaction with host cells. Finally, we demonstrated that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>ST41\/44 strains producing the mutated form did not induce killing mediated by NhhA-specific bactericidal antibodies. Our data help to elucidate the secretion mechanisms of trimeric autotransporters and to understand the contribution of NhhA in the evolutionary process of host-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria<\/jats:named-content>interactions. Also, they might have important implications for the evaluation of NhhA as a vaccine candidate.<\/jats:p>","DOI":"10.1128\/iai.00198-11","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T03:04:10Z","timestamp":1313463850000},"page":"4308-4321","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["A Naturally Occurring Single-Residue Mutation in the Translocator Domain of Neisseria meningitidis NhhA Affects Trimerization, Surface Localization, and Adhesive Capabilities"],"prefix":"10.1128","volume":"79","author":[{"given":"Hebert","family":"Echenique-Rivera","sequence":"first","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brunella","family":"Brunelli","sequence":"additional","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Scarselli","sequence":"additional","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Rita","family":"Taddei","sequence":"additional","affiliation":[{"name":"Centro Interdipartimentale di Microscopia Elettronica, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagrazia","family":"Pizza","sequence":"additional","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Aric\u00f2","sequence":"additional","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Serruto","sequence":"additional","affiliation":[{"name":"Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00718-10"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04423.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.24.3.330-332.1986"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.13.4026-4034.1999"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.03.004"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.13.4656-4664.2005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"5028","DOI":"10.4049\/jimmunol.160.10.5028","article-title":"Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid","volume":"160","author":"Granoff D. 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