{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T08:51:50Z","timestamp":1760345510746},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,1,18]],"date-time":"2002-01-18T00:00:00Z","timestamp":1011312000000},"content-version":"vor","delay-in-days":474,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:p>The acquisition of transition metal ions by pathogenic bacteria is crucial to their growth and survival within the human host, however, the mechanisms of metal ion homeostasis in streptococci are unknown. The <jats:italic>scaCBA<\/jats:italic> operon in the human oral bacterium <jats:italic>Streptococcus gordonii<\/jats:italic> encodes the components of an ABC\u2010type transporter for manganese (Mn<jats:sup>2+<\/jats:sup>). Production of substrate\u2010binding lipoprotein ScaA was increased approximately fivefold in cells cultured in low Mn<jats:sup>2+<\/jats:sup> medium (&lt;\u20030.1\u2003\u00b5M Mn<jats:sup>2+<\/jats:sup>), but not in iron (Fe<jats:sup>2+<\/jats:sup>\/Fe<jats:sup>3+<\/jats:sup>)\u2010limited medium, and was enhanced in the presence of human saliva or serum. mRNA analysis revealed that under low Mn<jats:sup>2+<\/jats:sup> conditions, levels of <jats:italic>scaCBA<\/jats:italic> transcript (2.6\u2003kb) were increased &gt;\u200a20\u2010fold. The Mn<jats:sup>2+<\/jats:sup>\u2010responsive transcriptional regulator of the <jats:italic>sca<\/jats:italic> operon was purified and characterized as a 215\u2010amino\u2010acid residue polypeptide, designated ScaR, with 26% identity to the <jats:italic>Corynebacterium diphtheriae<\/jats:italic> diphtheria toxin repressor (DtxR). Inactivation of <jats:italic>scaR<\/jats:italic> in <jats:italic>S. gordonii<\/jats:italic> DL1 (Challis) resulted in constitutive derepression of <jats:italic>sca<\/jats:italic> operon transcription. Expression of <jats:italic>tpx<\/jats:italic>, located immediately downstream of <jats:italic>scaA and<\/jats:italic> encoding a putative thiol peroxidase, was not subject to ScaR regulation. Purified ScaR protein bound to the <jats:italic>scaC<\/jats:italic> promoter region <jats:italic>in vitro<\/jats:italic> in the presence of Mn<jats:sup>2+<\/jats:sup> (<jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub>\u223c 80\u2003nM) and, to a lesser extent, in the presence of Ni<jats:sup>2+<\/jats:sup> or Zn<jats:sup>2+<\/jats:sup>. The metalloregulator protein binding region was localized by DNA protection analysis to a 46\u2003bp sequence encompassing the \u221235 and \u221210 promoter signatures. This sequence was well conserved within the promoters of corresponding virulence\u2010related permease operons in other streptococci. The results identify a new Mn<jats:sup>2+<\/jats:sup>\u2010sensing regulator of Mn<jats:sup>2+<\/jats:sup> transport in streptococci, important for Mn<jats:sup>2+<\/jats:sup> homeostasis during infection of the human host.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2000.02122.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:33:21Z","timestamp":1047468801000},"page":"140-153","source":"Crossref","is-referenced-by-count":105,"title":["Expression of the virulence\u2010related Sca (Mn<sup>2+<\/sup>) permease in <i>Streptococcus gordonii<\/i> is regulated by a diphtheria toxin metallorepressor\u2010like protein ScaR"],"prefix":"10.1111","volume":"38","author":[{"given":"Nicholas S.","family":"Jakubovics","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony W.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard 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