Pili are filamentous projections that traverse the outer membrane of the organism and are composed of repeating protein subunits (pilin) that help gonococci attach to mucosal surfaces by binding to the host cell receptor CD46 (13). Attachment is also mediated by a family of outer membrane proteins, designated opacity proteins, which bind to either CD66 or heparin-like molecules on host cells. Attachment and invasion of host epithelium are influenced by antigenic variations of pili and opacity proteins and by variations in the core sugars of lipooligosaccharide (LOS) components of the organism's outer membrane. These variations also help the organism evade the immune response.

When N. gonorrhoeae is grown on translucent agar, various colonial morphologies can be seen. Fresh clinical isolates initially form colony types P+ and P++ (formerly called T1 and T2). These organisms have numerous pili extending from the cell surface. After 20 to 24 hours, P— (formerly T3 and T4) colonies—in which the cells are nonpiliated—predominate. These nonpiliated organisms are not virulent. The shift between P+ or P++ and P- colony types is termed "phase variation" and is mediated by chromosomal rearrangement. The protein that constitutes pili (pilin) has regions of considerable antigenic variability between strains of N. gonorrhoeae. Single strains of N. gonorrhoeae also can produce pili of different antigenic composition (antigenic variation), which has made the possibility of a pilus-based vaccine against N. gonorrhoeae less feasible. Piliated gonococci are better able to attach to human mucosal surfaces than nonpiliated organisms. Pili also contribute to killing by neutrophils.

Typical urethral infections result in moderately severe inflammation, probably due to the release of toxic lipopolysaccharide and peptidoglycan fragments and to chemotactic factors that attract neutrophilic leukocytes. The reasons that some gonococcal strains selectively cause asymptomatic genital infection are poorly understood, but this propensity may be related to differences in the ability of the organism to bind complement-regulatory proteins that downregulate the production of chemotactic peptides.

The gonococcus has a cell envelope like other Gram-negative bacteria; it consists of three layers: an inner cytoplasmic membrane, a middle peptidoglycan cell wall, and an outer membrane. The outer membrane contains LOS, phospholipid, and a variety of proteins. One of them is protein I, which functions as a porin and is believed to play an important role in pathogenesis. Preliminary data suggest that it may facilitate endocytosis of the organism or otherwise trigger invasion. Protein I is also the basis of the most commonly used gonococcal serotyping system because there is consistent antigenic variation between different strains. Certain N. gonorrhoeae protein I serovars are associated with resistance of the organism to the bactericidal effect of normal nonimmune serum and an increased propensity to cause bacteremia. Gonococcal LOS is an endotoxin that differs from the polysaccharides of most Gram-negative bacteria in that it lacks O-antigenic side chains. Some components of LOS are also related to resistance of N. gonorrhoeae to serum bactericidal activity. LOS also demonstrates interstrain antigenic variations, which are the basis of another serotyping system.

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