Home LiteratureArticle Details
PMID: 10899841 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Genetic characterization of a Streptococcus mutans LraI family operon and role in virulence.

Infection and immunity ·Vol. 68 ·No. 8 ·2000-08-00 ·Pages 4441-51

Kitten T, Munro CL, Michalek SM, Macrina FL

Abstract

Proteins belonging to the LraI (for "lipoprotein receptor antigen") family function as adhesins in several streptococci, as a virulence factor for endocarditis in at least one of these species, and potentially as metal transporters in many bacteria. We have identified and characterized the chromosomal locus containing the LraI family gene (designated sloC) from Streptococcus mutans, an agent of dental caries and endocarditis in humans. Northern blot analysis indicated that sloC is cotranscribed with three other genes. As with other LraI operons, the sloA and sloB genes apparently encode components of an ATP-binding cassette transport system. The product of the fourth gene, sloR, has homology to the metal-dependent regulator from Corynebacterium diphtheriae, DtxR. A potential binding site for SloR was identified upstream from the sloABCR operon and was conserved upstream from LraI operons in several other streptococci. Potential SloR homologs were identified in the unfinished genomic sequences from two of these, S. pneumoniae and S. pyogenes. Mutagenesis of sloC in S. mutans resulted in apparent loss of expression of the entire operon as assessed by Northern blot analysis. The sloC mutant was indistinguishable from its wild-type parent in a gnotobiotic rat model of caries but was significantly less virulent in a rat model of endocarditis. Virulence for endocarditis was restored by correction of the sloC mutation but not by provision of the sloC gene in trans, suggesting that virulence requires the expression of other genes in the sloC operon.

MeSH Terms
ATP-Binding Cassette Transporters/genetics Adhesins, Bacterial/genetics Amino Acid Sequence Animals Base Sequence Cloning, Molecular Dental Caries/microbiology Genes, Bacterial Genes, Regulator Genetic Complementation Test Germ-Free Life Molecular Sequence Data Operon Rats Sequence Analysis, DNA Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Streptococcus mutans/genetics,pathogenicity Virulence/genetics
Chemicals
ATP-Binding Cassette Transporters Adhesins, Bacterial
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kitten T
Philips Institute of Oral & Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298, USA. tkitten@hsc.vcu.edu
Munro C L
Michalek S M
Macrina F L
References (62)
62 references, click to expand
  1. Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor.
    Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12844-8 PMID: 10536010
  2. scbA from Streptococcus crista CC5A: an atypical member of the lraI gene family.
    Infect Immun. 1996 Jun;64(6):2114-21 PMID: 8675315
  3. Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.
    Science. 1999 Nov 19;286(5444):1571-7 PMID: 10567266
  4. Virulence of Streptococcus mutans: a sensitive method for evaluating cariogenicity in young gnotobiotic rats.
    Infect Immun. 1975 Jul;12(1):69-75 PMID: 1140853
  5. Indirect selection of bacterial plasmids lacking identifiable phenotypic properties.
    J Bacteriol. 1975 Oct;124(1):225-31 PMID: 1100600
  6. Biology, immunology, and cariogenicity of Streptococcus mutans.
    Microbiol Rev. 1980 Jun;44(2):331-84 PMID: 6446023
  7. A cloning vector able to replicate in Escherichia coli and Streptococcus sanguis.
    Gene. 1982 Oct;19(3):345-53 PMID: 6295886
  8. Novel shuttle plasmid vehicles for Escherichia-Streptococcus transgeneric cloning.
    Gene. 1983 Nov;25(1):145-50 PMID: 6319229
  9. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
    EMBO J. 1982;1(8):945-51 PMID: 6329717
  10. Binding of manganese in human and rat plasma.
    Biochim Biophys Acta. 1985 Jun 18;840(2):163-9 PMID: 3995083
  11. Sequence of gene malG in E. coli K12: homologies between integral membrane components from binding protein-dependent transport systems.
    EMBO J. 1985 Sep;4(9):2287-93 PMID: 3000770
  12. Characterization of genetic transformation in Streptococcus mutans by using a novel high-efficiency plasmid marker rescue system.
    J Bacteriol. 1986 May;166(2):658-65 PMID: 3009419
  13. Transformation of Streptococcus mutans with chromosomal and shuttle plasmid (pYA629) DNAs.
    Infect Immun. 1986 Nov;54(2):273-82 PMID: 3021626
  14. Cloning of a Streptococcus sanguis adhesin which mediates binding to saliva-coated hydroxyapatite.
    Infect Immun. 1988 May;56(5):1150-7 PMID: 3356463
  15. Evidence for high affinity binding-protein dependent transport systems in gram-positive bacteria and in Mycoplasma.
    EMBO J. 1988 Dec 1;7(12):3971-4 PMID: 3208757
  16. Biochemical characterization and evaluation of virulence of a fructosyltransferase-deficient mutant of Streptococcus mutans V403.
    Infect Immun. 1989 Nov;57(11):3560-9 PMID: 2807537
  17. The ami locus of the gram-positive bacterium Streptococcus pneumoniae is similar to binding protein-dependent transport operons of gram-negative bacteria.
    Mol Microbiol. 1990 Apr;4(4):633-44 PMID: 2352474
  18. Molecular cloning and DNA sequence analysis of a diphtheria tox iron-dependent regulatory element (dtxR) from Corynebacterium diphtheriae.
    Proc Natl Acad Sci U S A. 1990 Aug;87(15):5968-72 PMID: 2116013
  19. Characterization of Streptococcus gordonii (S. sanguis) PK488 adhesin-mediated coaggregation with Actinomyces naeslundii PK606.
    Infect Immun. 1990 Sep;58(9):3064-72 PMID: 2387635
  20. Prediction of rho-independent Escherichia coli transcription terminators. A statistical analysis of their RNA stem-loop structures.
    J Mol Biol. 1990 Dec 20;216(4):835-58 PMID: 1702475
  21. Nucleotide sequence of a gene coding for a saliva-binding protein (SsaB) from Streptococcus sanguis 12 and possible role of the protein in coaggregation with actinomyces.
    Infect Immun. 1991 Mar;59(3):1093-9 PMID: 1671775
  22. Cariogenicity of Streptococcus mutans V403 glucosyltransferase and fructosyltransferase mutants constructed by allelic exchange.
    Infect Immun. 1991 Jul;59(7):2316-23 PMID: 1828790
  23. Specific binding of the diphtheria tox regulatory element DtxR to the tox operator requires divalent heavy metal ions and a 9-base-pair interrupted palindromic sequence.
    Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5897-901 PMID: 1631071
  24. Binding of the metalloregulatory protein DtxR to the diphtheria tox operator requires a divalent heavy metal ion and protects the palindromic sequence from DNase I digestion.
    J Biol Chem. 1992 Oct 25;267(30):21761-4 PMID: 1400485
  25. Saliva-binding protein (SsaB) from Streptococcus sanguis 12 is a lipoprotein.
    J Bacteriol. 1993 Jan;175(2):572-4 PMID: 8419308
  26. Overexpression and purification of a fimbria-associated adhesin of Streptococcus parasanguis.
    Infect Immun. 1993 Mar;61(3):1016-22 PMID: 8094376
  27. MsmE, a lipoprotein involved in sugar transport in Streptococcus mutans.
    J Bacteriol. 1993 Mar;175(6):1853-5 PMID: 8449892
  28. Sucrose-derived exopolysaccharides of Streptococcus mutans V403 contribute to infectivity in endocarditis.
    Mol Microbiol. 1993 Apr;8(1):133-42 PMID: 8497189
  29. Cysteine-102 is positioned in the metal binding activation site of the Corynebacterium diphtheriae regulatory element DtxR.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8524-8 PMID: 8378326
  30. Analysis of diphtheria toxin repressor-operator interactions and characterization of a mutant repressor with decreased binding activity for divalent metals.
    Mol Microbiol. 1993 Jul;9(1):173-81 PMID: 8412663
  31. Genetic analysis of fructan-hyperproducing strains of Streptococcus mutans.
    Infect Immun. 1994 Jul;62(7):2679-86 PMID: 7911782
  32. Cell surface protein receptors in oral streptococci.
    FEMS Microbiol Lett. 1994 Aug 15;121(2):133-40 PMID: 7926661
  33. Iron, DtxR, and the regulation of diphtheria toxin expression.
    Mol Microbiol. 1994 Oct;14(2):191-7 PMID: 7830565
  34. TopPred II: an improved software for membrane protein structure predictions.
    Comput Appl Biosci. 1994 Dec;10(6):685-6 PMID: 7704669
  35. Molecular identification of an ABC transporter complex for manganese: analysis of a cyanobacterial mutant strain impaired in the photosynthetic oxygen evolution process.
    EMBO J. 1995 May 1;14(9):1845-53 PMID: 7743991
  36. Recovery of RNA from oral streptococci.
    Biotechniques. 1995 Mar;18(3):412-4 PMID: 7540019
  37. Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats.
    Infect Immun. 1997 Mar;65(3):994-1002 PMID: 9038308
  38. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  39. Determination of the transcript size and start site of the putative sca operon of Streptococcus gordonii ATCC 51656 (formerly strain PK488).
    Adv Exp Med Biol. 1997;418:657-60 PMID: 9331737
  40. Identification and transcriptional analysis of a Treponema pallidum operon encoding a putative ABC transport system, an iron-activated repressor protein homolog, and a glycolytic pathway enzyme homolog.
    Gene. 1997 Sep 15;197(1-2):47-64 PMID: 9332349
  41. Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterization.
    J Bacteriol. 1997 Oct;179(20):6228-37 PMID: 9335267
  42. Competence and virulence of Streptococcus pneumoniae: Adc and PsaA mutants exhibit a requirement for Zn and Mn resulting from inactivation of putative ABC metal permeases.
    Mol Microbiol. 1997 Aug;25(4):727-39 PMID: 9379902
  43. The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn2+ uptake.
    J Bacteriol. 1998 Jan;180(2):290-5 PMID: 9440518
  44. The Escherichia coli ATP-binding cassette (ABC) proteins.
    Mol Microbiol. 1998 Apr;28(1):5-13 PMID: 9593292
  45. Molecular cloning of a 32-kilodalton lipoprotein component of a novel iron-regulated Staphylococcus epidermidis ABC transporter.
    Infect Immun. 1998 Aug;66(8):3767-74 PMID: 9673260
  46. SirR, a novel iron-dependent repressor in Staphylococcus epidermidis.
    Infect Immun. 1998 Sep;66(9):4123-9 PMID: 9712757
  47. The adc locus, which affects competence for genetic transformation in Streptococcus pneumoniae, encodes an ABC transporter with a putative lipoprotein homologous to a family of streptococcal adhesins.
    Res Microbiol. 1997 Feb;148(2):119-31 PMID: 9765793
  48. Penicillin tolerance genes of Streptococcus pneumoniae: the ABC-type manganese permease complex Psa.
    Mol Microbiol. 1998 Sep;29(5):1285-96 PMID: 9767595
  49. Prevention of bacterial endocarditis: highlights of the latest recommendations by the American Heart Association.
    Pediatr Infect Dis J. 1998 Sep;17(9):824-5 PMID: 9779771
  50. The PROSITE database, its status in 1999.
    Nucleic Acids Res. 1999 Jan 1;27(1):215-9 PMID: 9847184
  51. Lmb, a protein with similarities to the LraI adhesin family, mediates attachment of Streptococcus agalactiae to human laminin.
    Infect Immun. 1999 Feb;67(2):871-8 PMID: 9916102
  52. Anion-coordinating residues at binding site 1 are essential for the biological activity of the diphtheria toxin repressor.
    Infect Immun. 1999 Apr;67(4):1806-11 PMID: 10085021
  53. Concentrations of trace elements in sera of newborns, young infants, and adults.
    Biol Trace Elem Res. 1999 May;68(2):121-35 PMID: 10327023
  54. Membrane topology of MntB, the transmembrane protein component of an ABC transporter system for manganese in the cyanobacterium Synechocystis sp. strain PCC 6803.
    J Bacteriol. 1999 Jun;181(11):3591-3 PMID: 10348875
  55. Trace elements and electrolytes in human resting mixed saliva after exercise.
    Br J Sports Med. 1999 Jun;33(3):204-7 PMID: 10378074
  56. Characterization of a manganese-dependent regulatory protein, TroR, from Treponema pallidum.
    Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10887-92 PMID: 10485921
  57. Nucleotide sequence of the Streptococcus gordonii PK488 coaggregation adhesin gene, scaA, and ATP-binding cassette.
    Infect Immun. 1994 Oct;62(10):4469-80 PMID: 7927711
  58. The fimA locus of Streptococcus parasanguis encodes an ATP-binding membrane transport system.
    Mol Microbiol. 1995 Mar;15(5):849-63 PMID: 7596287
  59. PCR-mediated recombination and mutagenesis. SOEing together tailor-made genes.
    Mol Biotechnol. 1995 Apr;3(2):93-9 PMID: 7620981
  60. FimA, a major virulence factor associated with Streptococcus parasanguis endocarditis.
    Infect Immun. 1995 Dec;63(12):4669-74 PMID: 7591121
  61. Identification of the primary metal ion-activation sites of the diphtheria tox repressor by X-ray crystallography and site-directed mutational analysis.
    Nat Struct Biol. 1996 Apr;3(4):382-7 PMID: 8599765
  62. Identification and characterization of a Streptococcus pyogenes ABC transporter with multiple specificity for metal cations.
    Mol Microbiol. 1999 Nov;34(3):596-606 PMID: 10564500
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
Published
2000-08-00
Pages
4441-51
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC98344
Subset
IM
Grants
NIDCR NIH HHS · DE08182 · United States
NIDCR NIH HHS · DE04224 · United States
NIDCR NIH HHS · R01 DE009081 · United States
NIDCR NIH HHS · R01 DE008182 · United States
NIDCR NIH HHS · DE09081 · United States
Databases
GENBANK
AF232688
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com