A Neisseria gonorrhoeae immunoglobulin A1 protease mutant is infectious inthe human challenge model of urethral infection

Many mucosal pathogens, including Neisseria gonorrhoeae, produce proteases that cleave immunoglobulin A (IgA), the predominant immunoglobulin class pr oduced at mucosal surfaces. While considerable circumstantial evidence sugg ests that IgA1 protease contributes to gonococcal virulence, there is no di rect evidence that N. gonorrhoeae requires IgA1 protease activity to infect a human host. We constructed a N. gonorrhoeae iga mutant without introduci ng new antibiotic resistance markers into the final mutant strain and used human experimental infection to test the ability of the mutant to colonize the male urethra and to cause gonococcal urethritis. Four of the five male volunteers inoculated with the Iga(-) mutant became infected. In every resp ect-clinical signs and symptoms, incubation period between inoculation and infection, and the proportion of volunteers infected-the outcome of human e xperimental infection with FA1090iga was indistinguishable from that previo usly reported for a variant of parent strain FA1090 matching the mutant in expression of Opa proteins, lipooligosaccharide, and pilin. These results i ndicate that N. gonorrhoeae does not require IgA1 protease production to ca use experimental urethritis in males.