Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University , Yangzhou , People's Republic of China.
Jiangsu Key Laboratory of Zoonosis, Yangzhou University , Yangzhou , People's Republic of China.
Emerg Microbes Infect. 2019;8(1):1254-1264. doi: 10.1080/22221751.2019.1660233.
Transition metals are nutrients essential for life. However, an excess of metals can be toxic to cells, and host-imposed metal toxicity is an important mechanism for controlling bacterial infection. Accordingly, bacteria have evolved metal efflux systems to maintain metal homeostasis. Here, we established that PmtA functions as a ferrous iron [Fe(II)] and cobalt [Co(II)] efflux pump in , an emerging zoonotic pathogen responsible for severe infections in both humans and pigs. expression is induced by Fe(II), Co(II), and nickel [Ni(II)], whereas PmtA protects against Fe(II) and ferric iron [Fe(III)]-induced bactericidal effect, as well as Co(II) and zinc [Zn(II)]-induced bacteriostatic effect. In the presence of elevated concentrations of Fe(II) and Co(II), Δ accumulates high levels of intracellular iron and cobalt, respectively. Δ is also more sensitive to streptonigrin, a Fe(II)-activated antibiotic. Furthermore, growth defects of Δ under Fe(II) or Co(II) excess conditions can be alleviated by manganese [Mn(II)] supplementation. Finally, PmtA plays a role in tolerance to HO-induced oxidative stress, yet is not involved in the virulence of in mice. Together, these data demonstrate that PmtA acts as a Fe(II) and Co(II) efflux pump, and contributes to oxidative stress resistance.
过渡金属是生命所必需的营养物质。然而，过量的金属对细胞是有毒的，宿主施加的金属毒性是控制细菌感染的重要机制。因此，细菌已经进化出金属外排系统来维持金属内稳态。在这里，我们证实 PmtA 在 中作为亚铁[Fe(II)]和钴[Co(II)]外排泵发挥作用， 是一种新兴的人畜共患病病原体，可导致人类和猪的严重感染。 表达受 Fe(II)、Co(II)和镍[Ni(II)]诱导，而 PmtA 可保护 免受 Fe(II)和高铁[Fe(III)]诱导的杀菌作用以及 Co(II)和锌[Zn(II)]诱导的抑菌作用。在 Fe(II)和 Co(II)浓度升高的情况下，Δ分别积累大量的细胞内铁和钴。Δ对链黑菌素（一种 Fe(II)激活的抗生素）也更敏感。此外，Mn(II)补充可缓解 Fe(II)或 Co(II)过量条件下 Δ 的生长缺陷。最后，PmtA 在耐受 HO 诱导的氧化应激中发挥作用，但不参与 在小鼠中的毒力。总之，这些数据表明 PmtA 作为 Fe(II)和 Co(II)外排泵发挥作用，并有助于抵抗氧化应激。
