Resistance to peroxynitrite in Neisseria gonorrhoeae

Abstract

Neisseria gonorrhoeaeencodes a number of important genes that aid in survival during times of oxidative stress. The same immune cells capable of oxygen-dependent killing mechanisms also have the capacity to generate reactive nitrogen species (RNS) that may function antimicrobially. F62 and eight additional gonococcal strains displayed a high level of resistance to peroxynitrite, whileNeisseria meningitidisandEscherichia colishowed a four- to seven-log and a four-log decrease in viability, respectively. Mutation of gonococcal orthologues that are known or suspected to be involved in RNS defence in other bacteria (ahpC, dnrNandmsrA) resulted in no loss of viability, suggesting thatN. gonorrhoeaehas a novel mechanism of resistance to peroxynitrite. Whole-cell extracts of F62 prevented the oxidation of dihydrorhodamine, and decomposition of peroxynitrite was not dependent onahpC, dnrNormsrA. F62 grown in co-culture withE. colistrain DH10B was shown to protectE. coliviability 10-fold. Also, peroxynitrite treatment of F62 did not result in accumulation of nitrated proteins, suggesting that an active peroxynitrite reductase is responsible for peroxynitrite decomposition rather than a protein sink for amino acid modification.