Contribution of Neisseria Gonorrhoeae Catalase in Defense Against Toxic Oxygen Radicals and Neutrophils, and Its Role During Experimental Genital Tract Infection of Mice

摘要

Neisseria gonorrhoeae (GC) is responsible for a variety of sexually transmitted mucosal infections including urethritis and cervicitis. The hallmark of symptomatic gonorrhea is an intense inflammatory response characterized by an influx of neutrophils (PMNs). The mechanism by which GC resists PMN defenses is not known, however it is hypothesized from in vitro studies that gonococcal catalase protects GC by breaking down H2O2 produced by PMNs during the oxidative burst. The primary objective of this research was to assess the role of gonococcal catalase in GC pathogenesis using a genetically defined catalase mutant in in vitro assays and in an animal infection model. The kat gene of GC strain FA1090 was sequenced and the nucleotide sequence was predicted to encode a 57 kDa (504 amino acid) protein. A GC kat mutant was constructed by allelic exchange and demonstrated to be more sensitive to H2O2 and paraquat, an inducer of toxic oxygen radicals, than the wild type (WT) parental strain. The kat mutant was also more sensitive to H2O2-producing commensal lactobacilli in vitro. Complementation of the catalase mutation in trans restored wild type levels of catalase activity, and resistance to paraquat and H2O2-producing lactobacilli, but not resistance to H2O2. The inability to complement the mutant fully is perhaps due to a modification in the recombinant protein as evidenced by an altered mobility of the recombinant catalase on activity gels.