Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male.

The opacity (Opa) proteins of Neisseria gonorrhoeae are a family of outer membrane proteins demonstrating phase and antigenic variation. N. gonorrhoeae strain FA0190 has 11 opa loci that encode at least 8 antigenically distinct Opa proteins. To determine if expression of one Opa protein or a subset of them is favored during gonococcal infection, we inoculated Opa-negative variants of strain FA1090 intraurethrally into male volunteers. The Opa phenotype of gonococci isolated from urine and urethral swab cultures from nine infected subjects was determined. Opa proteins were expressed in a large proportion of the reisolates from the infected subjects. Gonococci cultured from urine or urethral swab samples from six of the subjects were uniformly Opa positive, with the predominant Opa variants differing among subjects. Three different Opa proteins were represented as the predominant type in at least one subject each. In three subjects, there was more heterogeneity in Opa phenotype of the reisolates, including the presence of Opa-negative variants. An increase in the proportion of isolates expressing multiple Opa proteins occurred over time in most subjects. Passage of the inoculum in vitro did not result in similar changes in Opa expression. There was no detectable difference in infectivity of an Opa-negative variant and one expressing an Opa protein (OpaF) that was highly represented in reisolates from the original nine subjects. Reisolates from three infected volunteers inoculated with the OpaF variant showed continued expression of OpaF alone or in conjunction with other Opa proteins. These results demonstrate that there is strong selection for expression of one or more Opa proteins by strain FA1090 in vivo, but that no single protein is preferentially expressed during early infection in the male urethra.

Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development.

Neisseria gonorrhoeae infection is limited to the human host. Experimental urethral infection in male volunteers was used to study different aspects of the infection. Urethral installation of a variety of gonococcal variants (10(4)-10(6)) led to infection in 27 subjects, who developed pyuria and shed bacteria in urine before urethritis developed 1-6 days after gonococcal inoculation. The incubation period was affected by the inoculation procedure and size of the inoculum. Subjects were treated with intramuscular ceftriaxone (250 mg) if urethritis developed or at 6 days after inoculation. Urine cultures became negative within several hours of therapy, and symptoms resolved within 1 day of therapy. Infected patients suffered no major complications. Experimental male urethral gonococcal infection provides a unique opportunity to understand the biology and immunology of gonococcal infection and is an efficient method to test gonococcal vaccine candidates.