{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:29:03Z","timestamp":1777577343217,"version":"3.51.4"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"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":[[2012,2]]},"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>binds the complement downregulating protein, factor H (fH), which enables the organism to evade host defenses. Two fH ligands, fHbp and NspA, are known to bind specifically to human fH. We developed a human fH transgenic infant rat model to investigate the effect of human fH on meningococcal bacteremia. At 18 h after intraperitoneal challenge with 560 CFU of group B strain H44\/76, all 19 human fH-positive rats had positive blood cultures compared to 0 of 7 human fH-negative control littermates (<jats:italic>P<\/jats:italic>&lt; 0.0001). Human fH-positive infant rats also developed bacteremia after challenge with isogenic mutants of H44\/76 in which genes encoding fHbp and NspA (\u0394fHbp \u0394NspA mutant) or the lipooligosaccharide sialyltransferase (\u0394<jats:italic>lst<\/jats:italic>mutant) had been inactivated. A fully encapsulated \u0394fHbp \u0394NspA \u0394<jats:italic>lst<\/jats:italic>mutant unable to sialylate lipooligosaccharide or bind human fH via the known fH ligands did not cause bacteremia, which argued against global susceptibility to bacteremia resulting from random integration of the transgene into the rat genome.<jats:italic>In vitro<\/jats:italic>, the wild-type and \u0394fHbp \u0394NspA mutant strains were killed by as little as 20% wild-type infant rat serum. The addition of 3 \u03bcg of human fH\/ml permitted survival of the wild-type strain in up to 60% infant rat serum, whereas \u226533 \u03bcg of human fH\/ml was required to rescue the \u0394fHbp \u0394NspA mutant. The ability of meningococci lacking expression of fHbp and NspA to cause invasive disease in human fH transgenic rats and to survive in wild-type infant rat serum supplemented with human fH indicates an additional human fH-dependent mechanism of evasion of innate immunity.<\/jats:p>","DOI":"10.1128\/iai.05604-11","type":"journal-article","created":{"date-parts":[[2011,11,22]],"date-time":"2011-11-22T07:00:38Z","timestamp":1321945238000},"page":"643-650","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Enhanced Bacteremia in Human Factor H Transgenic Rats Infected by Neisseria meningitidis"],"prefix":"10.1128","volume":"80","author":[{"given":"David M.","family":"Vu","sequence":"first","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutamas","family":"Shaughnessy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Granoff","sequence":"additional","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903598"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.01128\/mBio.00178\u2013111."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003470"},{"key":"e_1_3_3_5_2","first-page":"970","article-title":"Interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b, strain 44\/76-SL, before and after vaccination with the Norwegian MenBvac outer membrane vesicle vaccine","volume":"12","author":"Borrow R","year":"2005","unstructured":"BorrowR. 2005. 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