title: Manganese-dependent regulation of the endocarditis-associated virulence factor EfaA of Enterococcus faecalis.
abstract: There is increasing recognition of the emerging role of manganese regulation and acquisition in some pathogenic bacteria. Expression of the Enterococcus faecalis endocarditis-associated virulence factor EfaA is induced by growth in serum. It is demonstrated here that expression of the efaCBA operon encoding a putative ABC-type transporter is regulated by Mn(2+). Transcription of efaCBA and EfaA production were repressed in Mn(2+)-supplemented medium. A Mn(2+)-responsive transcriptional regulator, EfaR, sharing 27 % identity with the Corynebacterium diphtheriae diphtheria toxin repressor (DtxR), was identified. In the presence of Mn(2+), EfaR protein bound in vitro to the efaC promoter region. Analysis of the E. faecalis V583 genome revealed ten additional putative EfaR-binding sites, suggesting that manganese availability could have a broader regulatory role in infection. The results identify a new Mn(2+)-sensing regulator in enterococci that regulates the expression of a virulence factor implicated in enterococcal endocarditis.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK 2Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Yuen L
authors.initials: YL
authors.lastname: Low
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK 2Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Jakubovics
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK 2Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Flatman
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK 2Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Howard F
authors.initials: HF
authors.lastname: Jenkinson
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK 2Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000235:genetics / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000502:physiology; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D008345:Manganese / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; C116503:efaA protein, Enterococcus faecalis; D008345:Manganese