title: Regulation of Staphylococcus aureus MntC expression and its role in response to oxidative stress.
abstract: Staphylococcus aureus is a successful human pathogen that has developed several approaches to evade the immune system, including resistance strategies to prevent oxidative killing by immune cells. One mechanism by which this evasion occurs is by production of superoxide dismutase enzymes, which require manganese as a cofactor. Manganese is acquired by the manganese transporter MntABC. One component of this operon, MntC, has been proposed as a potential vaccine candidate due to its early in vivo expression and its ability to provide protection in preclinical models of staphylococcal infection. In the current study, we interrogate the role of this protein in protecting S. aureus from oxidative stress. We demonstrate that mutation of mntC in a number of invasive S. aureus clinical isolates results in increased sensitivity to oxidative stress. In addition, we show that while downregulation of mntC transcription is triggered upon exposure to physiological concentrations of manganese, MntC protein is still present on the bacterial surface at these same concentrations. Taken together, these results provide insight into the role of this antigen for the pathogen.
authors.affiliation: Pfizer Vaccine Research, Pearl River, New York, United States of America.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Handke
authors.forename: Julio C
authors.initials: JC
authors.lastname: Hawkins
authors.forename: Alita A
authors.initials: AA
authors.lastname: Miller
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008345:Manganese / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D008345:Manganese