PmtA functions as a ferrous iron and cobalt efflux pump in Streptococcus suis

Chengkun Zheng,Mengdie Jia,Miaomiao Gao,Tianyu Lu,Lingzhi Li,Pingping Zhou

doi:10.1080/22221751.2019.1660233

Chengkun Zheng, Mengdie Jia + Show 4 more

Open Access

https://doi.org/10.1080/22221751.2019.1660233

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Abstract

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 Streptococcus suis, an emerging zoonotic pathogen responsible for severe infections in both humans and pigs. pmtA expression is induced by Fe(II), Co(II), and nickel [Ni(II)], whereas PmtA protects S. suis 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), ΔpmtA accumulates high levels of intracellular iron and cobalt, respectively. ΔpmtA is also more sensitive to streptonigrin, a Fe(II)-activated antibiotic. Furthermore, growth defects of ΔpmtA 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 S. suis in mice. Together, these data demonstrate that S. suis PmtA acts as a Fe(II) and Co(II) efflux pump, and contributes to oxidative stress resistance.

Highlights

Transition metals such as iron, manganese, zinc, and copper are nutrients essential for life, and a variety of enzymes require a metal cofactor for their catalytic activity [1,2]
S. suis PmtA is a homolog of Fe(II) efflux pumps found in several gram-positive bacteria
We showed that MntE acts as a Mn(II) export system that contributes to S. suis virulence [23]

Summary

Introduction

Transition metals such as iron, manganese, zinc, and copper are nutrients essential for life, and a variety of enzymes require a metal cofactor for their catalytic activity [1,2]. Decreasing the availability of these metals plays an important role in the strategy used by the host immune system to limit bacterial growth [3]. Emerging evidence indicates that imposed metal toxicity is another host defense strategy against bacterial pathogens [1]. Neutrophils can mobilize zinc in response to Streptococcus pyogenes infection [5]. There is mounting evidence that metal homeostasis, maintained via metal efflux pumps, plays a critical role in bacterial physiology and pathogenesis [5,6,7,8,9,10,11]

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