title: The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes.
abstract: Streptococcus pyogenes(group AStreptococcus[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-regulatedmetaltransporterA), 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 5448ΔpmtAdeletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448ΔpmtAdeletion 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.
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Turner
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Cheryl-Lynn Y
authors.initials: CY
authors.lastname: Ong
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Karrera Y
authors.initials: KY
authors.lastname: Djoko
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: West
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.|Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Davies
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia mark.walker@uq.edu.au.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018384:Oxidative Stress; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics; D013308:Streptonigrin / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D013308:Streptonigrin; D006861:Hydrogen Peroxide; D007501:Iron; D000251:Adenosine Triphosphatases
keywords: PerR; PmtA; Streptococcus pyogenes; group A Streptococcus; iron efflux; oxidative stress response