{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:04:12Z","timestamp":1790316252385,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013473","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000}}],"reference-count":111,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI121015"],"award-info":[{"award-number":["1R01AI121015"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI172841"],"award-info":[{"award-number":["1R01AI172841"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE-1845298"],"award-info":[{"award-number":["DGE-1845298"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE-2236662"],"award-info":[{"award-number":["DGE-2236662"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE-1321851"],"award-info":[{"award-number":["DGE-1321851"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic><jats:italic>Kingella kingae<\/jats:italic><\/jats:italic> is a Gram-negative bacterium that has emerged as a leading cause of invasive disease in children between 6 months and 4 years of age. <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> initiates infection by colonizing the oropharynx, then breaches the oropharyngeal epithelium, enters the bloodstream, and disseminates to distant sites to cause disease, including osteomyelitis, septic arthritis, and endocarditis. To survive in the bloodstream and disseminate to sites of invasive disease, <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> produces a polysaccharide capsule and an exopolysaccharide that inhibit opsonin deposition and mediate resistance to complement-mediated serum killing. However, elimination of these extracellular polysaccharides only partially reduces <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> survival in human serum, suggesting that additional factors contribute to serum resistance. In this study, we found that <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> binds human factor H (FH), a negative regulator of the alternative complement pathway. In experiments using rat serum as a source of complement, we observed that <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> was able to utilize human FH to resist killing. Introduction of exogenous human FH into the juvenile rat infection model of <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> disease enhanced virulence in vivo, demonstrating the importance of FH binding in the pathogenesis of disease. Far-western blot analysis identified a 37-kDa outer membrane protein designated KK02920 that was responsible for FH binding and enhanced virulence in vivo in the presence of human FH. Loss of KK02920 virtually abrogated serum resistance, indicating that KK02920 is the major determinant of <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> serum resistance. Additional analysis revealed the presence of KK02920 across a collection of serum-resistant invasive and carrier <jats:italic><jats:italic>K. kingae<\/jats:italic><\/jats:italic> isolates, all of which can utilize human FH to resist complement-mediated killing. This work demonstrates the importance of a complement-regulator binding protein as a major mechanism of serum resistance in an encapsulated organism.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013473","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:57:41Z","timestamp":1756835861000},"page":"e1013473","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of a Kingella kingae factor H binding protein that is the major determinant of serum resistance"],"prefix":"10.1371","volume":"21","author":[{"given":"Kevin A.","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Porsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa 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