{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:23:22Z","timestamp":1792185802314,"version":"4.4.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"23","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI141181,AI132296,AI136007"],"award-info":[{"award-number":["AI141181,AI132296,AI136007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Research Foundation","award":["2018-02392"],"award-info":[{"award-number":["2018-02392"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,5]]},"abstract":"<jats:p>\n                    Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 porin B1a (PorB1a) and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96\/107 (89.7%) PorB1a and 16\/83 (19.3%) PorB1b bound C4BP; C4BP binding substantially correlated with the ability to evade complement-dependent killing (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.78). We designed 2 chimeric proteins that fused C4BP domains to the backbone of IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci (\n                    <jats:italic>\n                      K\n                      <jats:sub>D<\/jats:sub>\n                    <\/jats:italic>\n                    C4BP-IgM = 2.4 nM;\n                    <jats:italic>\n                      K\n                      <jats:sub>D<\/jats:sub>\n                    <\/jats:italic>\n                    C4BP-IgG 980.7 nM), but only hexameric C4BP-IgM efficiently outcompeted heptameric C4BP from the bacterial surface, resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM substantially attenuated the duration and burden of colonization of 2 C4BP-binding gonococcal isolates but not a non\u2013C4BP-binding strain in a mouse vaginal colonization model using human factor H\/C4BP\u2013transgenic mice. Our preclinical data present C4BP-IgM as an adjunct to conventional antimicrobials for the treatment of gonorrhea.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.131886","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T12:01:16Z","timestamp":1572350476000},"source":"Crossref","is-referenced-by-count":41,"title":["C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-4596","authenticated-orcid":true,"given":"Serena","family":"Bettoni","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-9954","authenticated-orcid":true,"given":"Jutamas","family":"Shaughnessy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Maziarz","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-9070","authenticated-orcid":true,"given":"David","family":"Ermert","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Gulati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-2898","authenticated-orcid":true,"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6212-6990","authenticated-orcid":true,"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[{"name":"Colzyx, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, \u00d6rebro University, \u00d6rebro, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6274-6965","authenticated-orcid":true,"given":"Kristian","family":"Riesbeck","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Unemo","sequence":"additional","affiliation":[{"name":"World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, \u00d6rebro University, \u00d6rebro, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, 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