Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress
Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress
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DOI：
10.1128/iai.06163-11
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发表时间：
2012-03-01
影响因子：
3.1
通讯作者：
McEwan, Alastair G.
中科院分区：
文献类型：
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作者：
Djoko, Karrera Y.;Franiek, Jessica A.;McEwan, Alastair G.
NGO0579在淋病奈瑟氏菌染色体中被注释为copA，这表明它编码对铜离子特异性的阳离子转运ATP酶。与野生型细胞相比，copA突变体对铜离子的杀伤更敏感，但对其他过渡金属则不敏感。该突变体还积累了更大量的铜，与CopA作为铜外排泵的预测作用一致。copA突变体表现出降低的能力，侵入和人类宫颈上皮细胞内的生存，虽然它的能力，这些细胞的表面上形成的生物膜是没有显着不同的野生型。在铜的存在下，copA突变体表现出增加的敏感性杀死亚硝酸盐或一氧化氮。因此，我们得出结论，CopA催化的铜离子流出与淋球菌的亚硝化应激防御系统有关。这些观察结果表明，铜可以发挥其作用，作为一种抗菌剂在先天免疫系统通过与活性氮物种的相互作用。
NGO0579 is annotated copA in the Neisseria gonorrhoeae chromosome, suggesting that it encodes a cation-transporting ATPase specific for copper ions. Compared to wild-type cells, a copA mutant 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. The copA mutant 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, the copA mutant 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 of Neisseria 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.