Abstract
Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pili, opacity proteins, IgA1 protease, and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea.
Highlights
In nature, gonococcal infection is strictly limited to the human host
Great care has been taken to describe and control the expression of recognized phase-variable determinants in experimental inocula. Inoculum variants of both strains used in the experimental infections included in the dose response analyses contained predominantly piliated (P+), Opacity protein-negative (Opa−) gonococci expressing the lacto-N -neotetraose LOS epitope recognized by monoclonal antibody (Mab) 3F11, which is associated with the development of urethral discharge in naturally acquired and experimental gonococcal infection in men (Schneider et al, 1991)
The rapid and uniform shift from Opa-negative to Opa protein expression by gonococci in the male urethra exhibited by both wild-type strains FA1090 and MS11mkC suggested that the capacity to express opacity proteins may be required during urethral infection, and an Opa-deficient FA1090 mutant was predicted to be attenuated in the human experimental model
Summary
Gonococcal infection is strictly limited to the human host. Uncomplicated infection can be asymptomatic or manifest as urethritis in men and cervicitis in women. Inoculum variants of both strains used in the experimental infections included in the dose response analyses contained predominantly piliated (P+), Opacity protein-negative (Opa−) gonococci expressing the lacto-N -neotetraose LOS epitope recognized by monoclonal antibody (Mab) 3F11, which is associated with the development of urethral discharge in naturally acquired and experimental gonococcal infection in men (Schneider et al, 1991).
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