Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

PmtA is a PerR-regulated ferrous iron efflux system of group A Streptococcus (#20)

Andrew G Turner 1 , Karrera Y Djoko 1 , Yanwen Cheryl-Lynn Ong 1 , Alastair G McEwan 1 , Mark J Walker 1
  1. University of Queensland, St. Lucia, QLD, Australia

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 the 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 intracellular Fe(II) compared to the wild-type and 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 a Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen. The interplay of Fe(II) and other metals within this system will be discussed.