Gonococcal Nitric Oxide Reductase Is Encoded by a Single Gene, norB , Which Is Required for Anaerobic Growth and Is Induced by Nitric Oxide

Abstract

ABSTRACT The gene encoding a nitric oxide reductase has been identified in Neisseria gonorrhoeae . The norB gene product shares significant identity with the nitric oxide reductases in Ralstonia eutropha and Synechocystis sp. and, like those organisms, the gonococcus lacks a norC homolog. The gonococcal norB gene was found to be required for anaerobic growth, but the absence of norB did not dramatically decrease anaerobic survival. In a wild-type background, induction of norB expression was seen anaerobically in the presence of nitrite but not anaerobically without nitrite or aerobically. norB expression is not regulated by FNR or NarP, but a functional aniA gene (which encodes an anaerobically induced outer membrane nitrite reductase) is necessary for expression. When aniA is constitutively expressed, norB expression can be induced both anaerobically and aerobically, but only in the presence of nitrite, suggesting that nitric oxide, which is likely to be produced by AniA as a product of nitrite reduction, is the inducing agent. This was confirmed with the use of the nitric oxide donor, spermine-nitric oxide complex, in an aniA null background both anaerobically and aerobically. NorB is important for gonococcal adaptation to an anaerobic environment, a physiologically relevant state during gonococcal infection. The presence of this enzyme, which is induced by nitric oxide, may also have implications in immune evasion and immunomodulation in the human host.