PmtA functions as a ferrous iron and cobalt efflux pump in .

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.