title: Modification of lipooligosaccharide with phosphoethanolamine by LptA in Neisseria meningitidis enhances meningococcal adhesion to human endothelial and epithelial cells.
abstract: The lipooligosaccharide (LOS) of Neisseria meningitidis can be decorated with phosphoethanolamine (PEA) at the 4' position of lipid A and at the O-3 and O-6 positions of the inner core of the heptose II residue. The biological role of PEA modification in N. meningitidis remains unclear. During the course of our studies to elucidate the pathogenicity of the ST-2032 (invasive) meningococcal clonal group, disruption of lptA, the gene that encodes the PEA transferase for 4' lipid A, led to a approximately 10-fold decrease in N. meningitidis adhesion to four kinds of human endothelial and epithelial cell lines at an multiplicity of infection of 5,000. Complementation of the lptA gene in a Delta lptA mutant restored wild-type adherence. By matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis, PEA was lost from the lipid A of the Delta lptA mutant compared to that of the wild-type strain. The effect of LptA on meningococcal adhesion was independent of other adhesins such as pili, Opc, Opa, and PilC but was inhibited by the presence of capsule. These results indicate that modification of LOS with PEA by LptA enhances meningococcal adhesion to human endothelial and epithelial cells in unencapsulated N. meningitidis.
authors.affiliation: Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan. hideyuki@nih.go.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Russel W
authors.initials: RW
authors.lastname: Carlson
authors.forename: Artur
authors.initials: A
authors.lastname: Muszynski
authors.forename: Biswa
authors.initials: B
authors.lastname: Choudhury
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D004983:Ethanolamines / Q000378:metabolism*; D006801:Humans; D008050:Lipid A / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009345:Neisseria meningitidis / Q000378:metabolism* / Q000472:pathogenicity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014166:Transferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004983:Ethanolamines; D008050:Lipid A; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; C005448:phosphorylethanolamine; D014166:Transferases