title: Growth of Neisseria gonorrhoeae in CMP-N-acetylneuraminic acid inhibits nonopsonic (opacity-associated outer membrane protein-mediated) interactions with human neutrophils.
abstract: Gonococci possessing certain opacity-associated (Opa) outer membrane proteins adhere to and are phagocytosed by human neutrophils in the absence of serum. Recently, it has been shown that serum-sensitive strains of Neisseria gonorrhoeae possessing the appropriate lipooligosaccharide phenotype become serum resistant when grown in the presence of CMP-N-acetylneuraminic acid (CMP-NANA) because of sialylation of their lipooligosaccharide. We investigated whether such sialylation affects nonopsonic (antibody- and complement-independent) interactions of gonococci with human neutrophils in vitro. We grew Opa+ gonococci in the presence of up to 50 micrograms of CMP-NANA per ml, incubated them with neutrophils in vitro, and measured their abilities to adhere to neutrophils, stimulate neutrophil luminol-dependent chemiluminescence (LDCL), and be phagocytically killed by neutrophils. Growth in CMP-NANA dramatically inhibited (in a dose-dependent manner) the ability of Opa+ gonococci to adhere to neutrophils and stimulate neutrophil LDCL. Growth of Opa+ gonococci in 50 micrograms of CMP-NANA per ml appeared to delay, but did not inhibit, their killing by neutrophils. Sialidase treatment of sialylated Opa+ gonococci, i.e., gonococci grown with CMP-NANA, totally restored their abilities to adhere to neutrophils and stimulate neutrophil LDCL. Opa- gonococci grown in the presence of 50 micrograms of CMP-NANA per ml and opsonized with fresh human serum bound to neutrophils only about 30% less efficiently than did Opa- gonococci grown without CMP-NANA and opsonized. The results of our studies show that sialylated Opa+ gonococci have dramatically reduced nonopsonic interactions with neutrophils. Some gonococcal strains may resist killing by human neutrophils in vivo by such a mechanism.
authors.affiliation: Department of Microbiology, Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102-1192.
authors.forename: R F
authors.initials: RF
authors.lastname: Rest
authors.forename: J V
authors.initials: JV
authors.lastname: Frangipane
mesh_terms: D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis*; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid