title: The lipooligosaccharide-modifying enzyme LptA enhances gonococcal defence against human neutrophils.
abstract: Infection with Neisseria gonorrhoeae (Gc) is marked by an influx of neutrophils to the site of infection. Despite a robust immune response, viable Gc can be recovered from neutrophil-rich gonorrhoeal secretions. Gc enzymatically modifies the lipid A portion of lipooligosaccharide by the addition of phosphoethanolamine to the phosphate group at the 4' position. Loss of lipooligosaccharide phosphoethanolamine transferase A (LptA), the enzyme catalysing this reaction, increases bacterial sensitivity to killing by human complement and cationic antimicrobial peptides. Here, we investigated the importance of LptA for interactions between Gc and human neutrophils. We found that lptA mutant Gc was significantly more sensitive to killing by human neutrophils. Three mechanisms underlie the increased sensitivity of lptA mutant Gc to neutrophils. (i) lptA mutant Gc is more likely to reside in mature phagolysosomes than LptA-expressing bacteria. (ii) lptA mutant Gc is more sensitive to killing by components found in neutrophil granules, including CAP37/azurocidin, human neutrophil peptide 1 and the serine protease cathepsin G. (iii) lptA mutant Gc is more susceptible to killing by antimicrobial components that are exocytosed from neutrophils, including those decorating neutrophil extracellular traps. By increasing the resistance of Gc to the bactericidal activity of neutrophils, LptA-catalysed modification of lipooligosaccharide enhances survival of Gc from the human inflammatory response during acute gonorrhoea.
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Handing
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Criss
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000378:metabolism*; D050296:Microbial Viability; D009344:Neisseria gonorrhoeae / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010588:Phagosomes / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D004798:Enzymes; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides