PmtA functions as a ferrous iron and cobalt efflux pump in <i>Streptococcus suis</i>

Abstract

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 <i>Streptococcus suis</i>, an emerging zoonotic pathogen responsible for severe infections in both humans and pigs. <i>pmtA</i> expression is induced by Fe(II), Co(II), and nickel [Ni(II)], whereas PmtA protects <i>S. suis</i> 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<i>pmtA</i> accumulates high levels of intracellular iron and cobalt, respectively. Δ<i>pmtA</i> is also more sensitive to streptonigrin, a Fe(II)-activated antibiotic. Furthermore, growth defects of Δ<i>pmtA</i> under Fe(II) or Co(II) excess conditions can be alleviated by manganese [Mn(II)] supplementation. Finally, PmtA plays a role in tolerance to H₂O₂-induced oxidative stress, yet is not involved in the virulence of <i>S. suis</i> in mice. Together, these data demonstrate that <i>S. suis</i> PmtA acts as a Fe(II) and Co(II) efflux pump, and contributes to oxidative stress resistance.