{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:36:06Z","timestamp":1773495366178,"version":"3.50.1"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The University of Iowa, Helen C. levitt Professorship"},{"name":"Australian Medical Research Council","award":["APP1071659"],"award-info":[{"award-number":["APP1071659"]}]},{"name":"Australian Medical Research Council","award":["APP1138466"],"award-info":[{"award-number":["APP1138466"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI024616"],"award-info":[{"award-number":["AI024616"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["015688"],"award-info":[{"award-number":["015688"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,9,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Nontypeable\n            <jats:named-content content-type=\"genus-species\">Haemophilus influenzae<\/jats:named-content>\n            (NTHi) is an important pathogen in individuals of all ages. The lipooligosaccharide (LOS) of NTHi has evolved a complex structure that can be attributed to a multiplicity of glycosyltransferases, the random switching of glycosyltransferase gene expression via phase variation, and the complex structure of its core region with multiple glycoform branch points. This article adds to that complexity by describing a multifunctional enzyme (LsgB) which optimally functions when the species is grown on a solid surface and which can add either a ketodeoxyoctanoate (KDO) or an\n            <jats:italic>N<\/jats:italic>\n            -acetylneuramic acid (Neu5Ac) moiety to a terminal\n            <jats:italic>N-<\/jats:italic>\n            acetyllactosamine structure of LOS. Our studies show that expression of\n            <jats:italic>lsgB<\/jats:italic>\n            is reduced four- to sixfold when NTHi is grown in broth. The substrate that the enzyme utilizes is dependent upon the concentration of free Neu5Ac (between 1 and 10\u00a0\u00b5g\/ml) in the environment. In environments in which Neu5Ac is below that level, the enzyme utilizes endogenous CMP-KDO as the substrate. Our studies show that during\n            <jats:italic>in vivo<\/jats:italic>\n            growth in an NTHi biofilm, the KDO moiety is expressed by the organism. Monoclonal antibody 6E4, which binds KDO, is bactericidal for NTHi strains that express the KDO epitope at high levels. In a survey of 33 NTHi strains isolated from healthy and diseased individuals, the antibody was bactericidal (&gt;90% kill) for 12 strains (36%). These studies open up the possibility of using a KDO-based glycoconjugate vaccine as part of a multicomponent vaccine against NTHi.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Nontypeable\n            <jats:named-content content-type=\"genus-species\">Haemophilus influenzae<\/jats:named-content>\n            is an important pathogen in middle ear infections in children, sinusitis in adults, and acute bronchitis in individuals with chronic obstructive lung disease. The organism is very well adapted to the human host environment, and this has hindered successful development of an effective vaccine. In this article, we describe a mechanism by which the bacteria decorates its surface lipooligosaccharide with a sugar unique to Gram-negative bacteria, ketodeoxyoctanoate (KDO). This sugar decoration is present during active infection and we have shown that an antibody directed against this sugar can result in killing of the organism. These data demonstrate that the lipooligosaccharide ketodeoxyoctanoate epitope may be a novel NTHi\n            <jats:italic>-<\/jats:italic>\n            specific candidate vaccine antigen.\n          <\/jats:p>","DOI":"10.1128\/mbio.01401-18","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T09:59:22Z","timestamp":1532944762000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Nontypeable Haemophilus influenzae Lipooligosaccharide Expresses a Terminal Ketodeoxyoctanoate\n            <i>In Vivo<\/i>\n            , Which Can Be Used as a Target for Bactericidal Antibody"],"prefix":"10.1128","volume":"9","author":[{"given":"Michael A.","family":"Apicella","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Coffin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Ketterer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah M. B.","family":"Post","sequence":"additional","affiliation":[{"name":"Buck Institute for Age Research, Novato, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Day","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freda E.-C.","family":"Jen","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Jennings","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408419609106458"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090505"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00492-13"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00132.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.2000.0477"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00212.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00140.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02666.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80352-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.4.1322-1328.1992"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1432026100"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3210-3218.2005"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-008-0014-y"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05890.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5291-5300.2005"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/227382a0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706603200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(89)90112-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110986200"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602314200"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02204.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/165-Supplement_1-S195"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb02092.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwq033"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.6.1558-1564.1990"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.7.4747"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-240"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2013.11.016"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01185-15"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01832-07"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.20.6455-6459.1992"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.1.107"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.2.506"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.5.1649"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(97)00472-6"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01522-9"},{"key":"e_1_3_3_38_2","first-page":"177","article-title":"Typing of group-B Neisseria meningitidis with monoclonal antibodies in the whole-cell ELISA","volume":"26","author":"Abdillahi H","year":"1988","unstructured":"Abdillahi H, Poolman JT. 1988. Typing of group-B Neisseria meningitidis with monoclonal antibodies in the whole-cell ELISA. J Med Microbiol 26:177\u2013180.","journal-title":"J Med Microbiol"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02601-14"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(84)90320-8"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.4.1377-1386.1997"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01401-18","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01401-18","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:52:57Z","timestamp":1646707977000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01401-18"}},"subtitle":[],"editor":[{"given":"Edward G.","family":"Ruby","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,9,5]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,9,5]]}},"alternative-id":["10.1128\/mBio.01401-18"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01401-18","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,5]]},"assertion":[{"value":"2018-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01401-18"}}