{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:43:22Z","timestamp":1790243002633,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lipooligosaccharide (LOS) of<jats:italic>Neisseria meningitidis<\/jats:italic>has been implicated in meningococcal interaction with host epithelial cells and is a major factor contributing to the human proinflammatory response to meningococci. LOS mutants of the encapsulated<jats:italic>N. meningitidis<\/jats:italic>serogroup B strain NMB were used to further determine the importance of the LOS structure in in vitro adherence and invasion of human pharyngeal epithelial cells by meningococci and to study pathogenicity in a mouse (CD46 transgenic) model of meningococcal disease. The wild-type strain [NeuNAc-Gal\u03b2-GlcNAc-Gal\u03b2-Glc\u03b2-Hep<jats:sub>2<\/jats:sub>(GlcNAc, Glc\u03b1) 3-deoxy-<jats:sc>d<\/jats:sc>-manno-2-octulosonic acid (KDO<jats:sub>2<\/jats:sub>)-lipid A; 1,4\u2032 bisphosphorylated], although poorly adherent, rapidly invaded an epithelial cell layer in vitro, survived and multiplied early in blood, reached the cerebrospinal fluid, and caused lethal disease in the mouse model. In contrast, the Hep<jats:sub>2<\/jats:sub>(GlcNAc) KDO<jats:sub>2<\/jats:sub>-lipid A (<jats:italic>pgm<\/jats:italic>) mutant, which was highly adherent to cultured epithelial cells, caused significantly less bacteremia and mortality in the mouse model. The Hep<jats:sub>2<\/jats:sub>-KDO<jats:sub>2<\/jats:sub>-lipid A (<jats:italic>rfaK<\/jats:italic>) mutant was shown to be moderately adherent and to cause levels of bacteremia and mortality similar to those caused by the wild-type strain in the mouse model. The KDO<jats:sub>2<\/jats:sub>-lipid A (<jats:italic>gmhB<\/jats:italic>) mutant, which lacks the heptose disaccharide in the inner core of LOS, avidly attached to epithelial cells but was otherwise avirulent. Disease development correlated with expression of specific LOS structures and was associated with lower adherence but rapid meningococcal passage to and survival in the bloodstream, induction of proinflammatory cytokines, and the crossing of the blood-brain barrier. Taken together, the results of this study further define the importance of the LOS structure as a virulence component involved in multiple steps in the pathogenesis of<jats:italic>N. meningitidis<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.74.2.1360-1367.2006","type":"journal-article","created":{"date-parts":[[2006,1,21]],"date-time":"2006-01-21T01:42:38Z","timestamp":1137807758000},"page":"1360-1367","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Lipooligosaccharide Structure Contributes to Multiple Steps in the Virulence of<i>Neisseria meningitidis<\/i>"],"prefix":"10.1128","volume":"74","author":[{"given":"Laura","family":"Plant","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Sundqvist","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"Zughaier","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Lo\u0308vkvist","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia"},{"name":"Laboratories of Microbial Pathogenesis, VA Medical Center, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Beth","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.2.507"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.1.155-162.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115660"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.2.195"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.8.2998-3006.1996"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48372-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02666.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1139\/o80-018"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086476"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.433"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(92)90022-G"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.5.1265-1273.1996"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwi018"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.12.5939-5947.1998"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408419891294216"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.85.6.1274-1279.1963"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S1016-8478(23)13731-9","volume":"15","year":"2003","unstructured":"Kim, C. 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