title: The Neisseria gonorrhoeae lpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses.
abstract: LPS is a fundamental constituent of the outer membrane of all Gram-negative bacteria, and the lipid A domain plays a central role in the induction of inflammatory responses. We identified genes of the Neisseria gonorrhoeae lipid A biosynthetic pathway by searching the complete gonococcal genome sequence with sequences of known enzymes from other species. The lpxLII gene was disrupted by an insertion-deletion in an attenuated aroA mutant of the gonococcal strain MS11. Lipopolysaccharide (LPS) and lipid A analysis demonstrated that the lpxLII mutant had synthesized an altered LPS molecule lacking a single lauric fatty acid residue in the GlcN II of the lipid A backbone. LPS of the lpxLII mutant had a markedly reduced ability to induce the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8 from human macrophages and IL-8 from polymorphonuclear cells. This study demonstrates that the lpxLII gene in gonococci encodes for a late-functioning lauroyl acyl transferase that adds a lauric acid at position 2' in the lipid A backbone. The presence of lauric acid at such a position appears to be crucial for the induction of full inflammatory responses by N. gonorrhoeae LPS.
authors.affiliation: Department of Microbiology and Immunology, University of Newcastle upon Tyne, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. c.d.ellis@ncl.ac.uk
authors.forename: C D
authors.initials: CD
authors.lastname: Ellis
authors.forename: B
authors.initials: B
authors.lastname: Lindner
authors.forename: C M
authors.initials: CM
authors.lastname: Anjam Khan
authors.forename: U
authors.initials: U
authors.lastname: Zähringer
authors.forename: R
authors.initials: R
authors.lastname: Demarco de Hormaeche
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002478:Cells, Cultured; D005798:Genes, Bacterial; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008050:Lipid A / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000201:enzymology / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism; D016415:Sequence Alignment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; D000217:Acyltransferases; C118473:LpxL protein, bacteria