Characterization of Serum Resistance of Neisseria gonorrhoeae that Disseminate

Abstract

Neisseria gonorrhoeae isolated from patients with disseminated infection (DGI) often resist complement (C′)-dependent killing by normal human serum (NHS) and less commonly by convalescent DGI serum. 7 of 10 NHS specimens completely inhibited killing of serum-resistant (ser^r) gonococci by convalescent or immune DGI serum. Immunoglobulin G (IgG) purified from NHS was shown to be the blocking agent. In addition, IgM (plus C′) purified from NHS was shown to be fivefold more effective (wt/wt) in killing serum-sensitive (ser^s) gonococci than equivalent amounts of IgM tested in the presence of IgG (whole serum). Although inhibition of NHS killing of ser^s gonococci required a 640% excess of IgG, only a 40% excess was required to block immune serum killing of ser^r gonococci. F(ab′)₂ prepared from IgG also blocked killing of ser^r gonococci by immune serum indicating antigenic specificity of blocking IgG. IgG immunoconcentrated against outer membrane protein (OMP) derived from ser^r gonococci showed 40-fold increased blocking activity over normal IgG (wt/wt) and lacked antibody activity directed against gonococcal lipopolysaccharide by ELISA. Using direct immunoabsorption of IgG with purified gonococcal OMP; ser^r-OMP was found sixfold more effective than ser^s-OMP in neutralizing the blocking of immune serum killing of ser^r gonococci, and 10-fold more effective in systems that used excess blocking IgG, NHS, and ser^s gonococci. Blocking IgG preabsorbed with whole ser^r gonococci lost 75% of its ability to block immune serum killing compared with no loss in this system using a similar absorption with ser^s gonococci. IgG purified from NHS contained fivefold higher titers of antibody against ser^r-OMP than ser^s-OMP by ELISA.