Growth of Neisseria Gonorrhoeae in CMP-N-acetylneuraminic Acid Inhibits Nonopsonic (opacity-associated Outer Membrane Protein-mediated) Interactions with Human Neutrophils

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.