The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

Turner, Andrew G.; Ong, Cheryl-lynn Y.; Djoko, Karrera Y.; West, Nicholas P.; Davies, Mark R.; McEwan, Alastair G.; Walker, Mark J.

Abstract

Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and, as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA (PerR-regulated metal transporter A), a P1B-4-type ATPase efflux pump, in invasive GAS M1T1 strain 5448. We reveal that PmtA functions as a ferrous iron [Fe(II)] efflux system. In the presence of high Fe(II) concentrations, the 5448ΔpmtA deletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448ΔpmtA deletion mutant also showed enhanced susceptibility to killing by the Fe-dependent antibiotic streptonigrin as well as increased sensitivity to hydrogen peroxide and superoxide. We suggest that the PerR-mediated control of Fe(II) efflux by PmtA is important for bacterial defense against oxidative stress. PmtA represents an exemplar for an Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen.

Citation

Turner, A. G., Ong, C. Y., Djoko, K. Y., West, N. P., Davies, M. R., McEwan, A. G., & Walker, M. J. (2017). The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes. Infection and Immunity, 85(6), Article e00140-17. https://doi.org/10.1128/iai.00140-17

• Journal Article Type: Article
• Acceptance Date: Mar 25, 2017
• Online Publication Date: Apr 3, 2017
• Publication Date: 2017-06
• Deposit Date: Sep 6, 2017
• Journal: Infection and Immunity
• Print ISSN: 0019-9567
• Electronic ISSN: 1098-5522
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 85
• Issue: 6
• Article Number: e00140-17
• DOI: https://doi.org/10.1128/iai.00140-17
• Public URL: https://durham-repository.worktribe.com/output/1350068