title: Phosphoethanolamine Modification of Neisseria gonorrhoeae Lipid A Reduces Autophagy Flux in Macrophages.
abstract: Autophagy, an ancient homeostasis mechanism for macromolecule degradation, performs an important role in host defense by facilitating pathogen elimination. To counteract this host defense strategy, bacterial pathogens have evolved a variety of mechanisms to avoid or otherwise dysregulate autophagy by phagocytic cells so as to enhance their survival during infection. Neisseria gonorrhoeae is a strictly human pathogen that causes the sexually transmitted infection, gonorrhea. Phosphoethanolamine (PEA) addition to the 4' position of the lipid A (PEA-lipid A) moiety of the lipooligosaccharide (LOS) produced by gonococci performs a critical role in this pathogen's ability to evade innate defenses by conferring decreased susceptibility to cationic antimicrobial (or host-defense) peptides, complement-mediated killing by human serum and intraleukocytic killing by human neutrophils compared to strains lacking this PEA decoration. Heretofore, however, it was not known if gonococci can evade autophagy and if so, whether PEA-lipid A contributes to this ability. Accordingly, by using murine macrophages and human macrophage-like phagocytic cell lines we investigated if PEA decoration of gonococcal lipid A modulates autophagy formation. We report that infection with PEA-lipid A-producing gonococci significantly reduced autophagy flux in murine and human macrophages and enhanced gonococcal survival during their association with macrophages compared to a PEA-deficient lipid A mutant. Our results provide further evidence that PEA-lipid A produced by gonococci is a critical component in the ability of this human pathogen to evade host defenses.
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center Decatur, Atlanta, Georgia, United States of America.|Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Susu M
authors.initials: SM
authors.lastname: Zughaier
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Kandler
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Balthazar
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center Decatur, Atlanta, Georgia, United States of America.|Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.|Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line / Q000382:microbiology; D018925:Chemokines / Q000378:metabolism; D004187:Disaccharides / Q000494:pharmacology; D004983:Ethanolamines; D054884:Host-Pathogen Interactions; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000378:metabolism / Q000472:pathogenicity*; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D013403:Sugar Phosphates / Q000494:pharmacology
chemical_list: D018925:Chemokines; D004187:Disaccharides; D004983:Ethanolamines; D008050:Lipid A; D013403:Sugar Phosphates; C512420:eritoran; C005448:phosphorylethanolamine