SELECTION OF OPA(-GONORRHOEAE BY LIMITED AVAILABILITY OF NORMAL HUMANSERUM() NEISSERIA)

Experimental infections of human male volunteers with Neisseria gonorr hoeae have provided valuable insights into the early stages of gonorrh eal disease. Bacterial variants expressing outer membrane opacity (Opa ) proteins appear to be selected from the inoculum during a period in which total recoverable numbers of bacteria decrease rapidly. This app arent survival advantage occurs simultaneously with the onset of an in flammatory response, characterized by local production of interleukin 6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since the inflammatory response may also result in the presence of serum factor s on the mucosal surface, we investigated the possibility that killing in normal human serum (NHS) leads to the selection of Opa(+) variants . We therefore studied killing of separate populations and mixtures of Opa(-) and Opa(+) N. gonorrhoeae MS11mk in NHS. Expression of an Opa protein conferred a survival advantage upon the organism; i.e., the Op a(+) variants were more serum resistant than their isogenic Opa(-) cou nterparts, resulting in a selection for Opa(+) phenotypes when a mixtu re of Opa(+) and Opa(-) gonococci (GC) was exposed to submaximal doses of NHS. This selection was observed in three different lipooligosacch aride (LOS) backgrounds, indicating that it was not due to a differenc e in LOS expression between Opa(-) and Opa(+) phenotypes. Incubation i n NHS of sialylated GC resulted in a similar selection for Opa(+) vari ants. The presence of normal human urine during the serum killing assa y had no effect on the selection phenomenon but drastically depleted N HS of bactericidal activity, which was found to be at least partly due to complement inhibition. The results suggest that serum killing may contribute to the transition from Opa(-) to Opa(+) phenotypes during t he early stages of infection of the male urethra.