title: Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage.
abstract: The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.
authors.affiliation: From the Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, California 94121, the Departments of Laboratory Medicine and.
authors.forename: Constance M
authors.initials: CM
authors.lastname: John
authors.affiliation: the Departments of Laboratory Medicine and.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Phillips
authors.affiliation: From the Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, California 94121.
authors.forename: Richard
authors.initials: R
authors.lastname: Din
authors.affiliation: From the Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, California 94121, the Departments of Laboratory Medicine and.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Liu
authors.affiliation: the Norwegian Institute of Public Health, P. O. Box 4404, Nydalen, 0403 Oslo, Norway, and.
authors.forename: Einar
authors.initials: E
authors.lastname: Rosenqvist
authors.affiliation: the Norwegian Institute of Public Health, P. O. Box 4404, Nydalen, 0403 Oslo, Norway, and.
authors.forename: E Arne
authors.initials: EA
authors.lastname: Høiby
authors.affiliation: the Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Stein
authors.affiliation: From the Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, California 94121, the Departments of Laboratory Medicine and gary.jarvis@ucsf.edu.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Jarvis
mesh_terms: D000215:Acylation; D000293:Adolescent; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity*; D002353:Carrier State / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology*; D045744:Cell Line, Tumor; D019295:Computational Biology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity*; D008585:Meningitis, Meningococcal / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology*; D008589:Meningococcal Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology*; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D038541:Neisseria meningitidis, Serogroup B / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D038542:Neisseria meningitidis, Serogroup C / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D009664:Norway; D010766:Phosphorylation; D018805:Sepsis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C023023:lipid-linked oligosaccharides
keywords: Neisseria meningitidis; acylation; bioinformatics; infection; lipid A; lipooligosaccharide; mass spectrometry (MS); phosphoethanolamine; phosphorylation; sialic acid