Phenotypic Characterization of acopAMutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress
NGO0579 is annotatedcopAin theNeisseria gonorrhoeaechromosome, suggesting that it encodes a cation-transporting ATPase specific for copper ions. Compared to wild-type cells, acopAmutant was more sensitive to killing by copper ions but not to other transition metals. The mutant also accumulated a greater amount of copper, consistent with the predicted role of CopA as a copper efflux pump. ThecopAmutant showed a reduced ability to invade and survive within human cervical epithelial cells, although its ability to form a biofilm on the surface of these cells was not significantly different from that of the wild type. In the presence of copper, thecopAmutant exhibited increased sensitivity to killing by nitrite or nitric oxide. Therefore, we concluded that copper ion efflux catalyzed by CopA is linked to the nitrosative stress defense system ofNeisseria gonorrhoeae. These observations suggest that copper may exert its effects as an antibacterial agent in the innate immune system via an interaction with reactive nitrogen species.