MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake co-ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.
IntroductionThe acquisition of metal ions is essential for the life of all organisms. During bacterial infection, the host restricts the availability of some metal ions, such as iron. With the exception of Borrelia burgdorferi (Posey and Gherardini, 2000), successful colonization requires that pathogenic bacteria overcome this iron limitation (Wooldridge and Williams, 1993). Although B. burgdorferi does not need iron, it has an obligate requirement for manganese (Mn) (Posey and Gherardini, 2000). Manganese uptake has recently been shown to be important for a number of other pathogens. Bacterial Nramp homologues, called MntH, are selective Mn transporters that play a role in the response to reactive oxygen species and may have a role in pathogenesis (Kehres et al., 2000;Makui et al., 2000). In addition, the ATP-binding cassette (ABC) family of Mn transporters (Claverys, 2001) was clearly shown to be important during infections caused by Enterococcus faecalis (Singh et al., 1998), Streptococcus pneumoniae and Streptococcus parasanguinis (Burnette-Curley et al., 1995;Berry and Paton, 1996) and Yersinia pestis (Bearden and Perry, 1999). Thus, Mn can be added to the in vivo growth requirements of many pathogens (Posey and Gherardini, 2000).In bacteria, specific cellular roles have been determined for Mn as a cofactor in enzymes for metabolism, catabolism, signal transduction and photosynthesis (reviewed by Yocum and Pecoraro, 1999;Jakubovics and Jenkinson, 2001). In addition, an enzymatic and a non-enzymatic role for Mn in the protection of the cell from oxidative stress has been described. Many bacteria, including Staphylococcus aureus (Clements et al., 1999;Valderas and Hart, 2001), contain a Mn-superoxide dismutase (SOD) that catalyses the reduction of superoxide radicals to produce H 2 O 2 . Furthermore, inactivation of sodA, which encodes Mn-SOD, reduces virulence of Strep. pneumoniae in a murine intranasal infection (Yesilkaya et al., 2000).Simple Mn(II) salts are known to catalyse the dismutation of superoxide radical (Archibald and Fridovich, 1981a,b;. A number of bacteria have been shown
SummaryThe Staphylococcus aureus DtxR-like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal-depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR-dependent manner, which cont...