A Strain-Specific Catalase Mutation and Mutation of the Metal-Binding Transporter Gene mntC Attenuate Neisseria gonorrhoeae In Vivo but Not by Increasing Susceptibility to Oxidative Killing by Phagocytes

The hallmark of gonorrhea is an intense inflammatory response that is characterized by polymorphonuclear leukocytes (PMNs) with intracellular gonococci. A redundancy of defenses may protectNeisseria gonorrhoeae from phagocyte-derived reactive oxygen species. Here we showed that a gonococcal catalase (kat ) mutant in strain MS11 was more sensitive to H2 O2 than mutants in cytochromec peroxidase (ccp ), methionine sulfoxide reductase (msrA ), or the metal-binding protein (mntC ) of the MntABC transporter.kat ccp andkat ccp mntC mutants were significantly more sensitive to H2 O2 than mutants in any single factor. None of the mutants showed increased susceptibility to murine PMNs. Recovery of themntC andkat ccp mntC mutants from the lower genital tract of BALB/c mice, but not thekat orkat ccp mutants, was significantly reduced relative to wild-type bacteria. Interestingly, unlike the MS11kat mutant, akat mutant of strain FA1090 was attenuated during competitive infection with wild-type FA1090 bacteria. The FA1090kat mutant and MS11mntC mutant were also attenuated in mice that are unable to generate a phagocytic respiratory burst. We conclude that inactivation of three well-characterized antioxidant genes (kat ,ccp , andmntC ) does not increase gonococcal susceptibility to the phagocytic respiratory burst during infection and that gonococcal catalase and the MntC protein confer an unidentified advantage in vivo. In the case of catalase, this advantage is strain specific. Finally, we also showed that anmsrA mutant of strain MS11 demonstrated delayed attenuation in BALB/c but not C57BL/6 mice. Therefore, MsrA/B also appears to play a role in infection that is dependent on host genetic background.