Many mucosal pathogens, including Neisseria gonorrhoeae, produce
proteases that cleave
immunoglobulin A (
IgA), the predominant
immunoglobulin class produced at mucosal surfaces. While considerable circumstantial evidence suggests that
IgA1 protease contributes to gonococcal virulence, there is no direct evidence that N. gonorrhoeae requires
IgA1 protease activity to infect a human host. We constructed a N. gonorrhoeae
iga mutant without introducing 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 respect-clinical signs and symptoms, incubation period between inoculation and
infection, and the proportion of volunteers infected-the outcome of human experimental
infection with FA1090iga was indistinguishable from that previously reported for a variant of parent strain FA1090 matching the mutant in expression of Opa
proteins, lipooligosaccharide, and
pilin. These results indicate that N. gonorrhoeae does not require
IgA1 protease production to cause experimental
urethritis in males.