Phosphoethanolamine Modification of Neisseria gonorrhoeae Lipid A Reduces Autophagy Flux in Macrophages

• Published in: PloS one 2015-12, Vol.10 (12), p.e0144347
• Main Authors: Zughaier, Susu M, Kandler, Justin L, Balthazar, Jacqueline T, Shafer, William M
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Apoptosis; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Autophagy - physiology; Biodegradation; Camps; Cell death; Cell Line - microbiology; Cell lines; Cell survival; Chemokines - metabolism; Complement system; Critical components; Decoration; Disaccharides - pharmacology; Ethanolamines; Females; Gonorrhea; Health aspects; Helicobacter pylori; Homeostasis; Host-Pathogen Interactions; Human performance; Humans; Immunology; Infections; Laboratories; Leukocytes (neutrophilic); Lipid A; Lipid A - chemistry; Lipid A - metabolism; Lipids; Macrophages; Macrophages - microbiology; Medicine; Metabolism; Mice; Mycobacterium tuberculosis; Neisseria gonorrhoeae; Neisseria gonorrhoeae - metabolism; Neisseria gonorrhoeae - pathogenicity; Neutrophils; Pathogenesis; Pathogens; Peptides; Phagocytes; Phagocytosis; Phagosomes - metabolism; Phagosomes - microbiology; Proteins; Sexually transmitted diseases; STD; Sugar Phosphates - pharmacology; Survival; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144347

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.