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PMID: 16790755 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

LuxS involvement in the regulation of genes coding for hemin and iron acquisition systems in Porphyromonas gingivalis.

Infection and immunity ·Vol. 74 ·No. 7 ·2006-07-00 ·Pages 3834-44

James CE, Hasegawa Y, Park Y, Yeung V, Tribble GD, Kuboniwa M, Demuth DR, Lamont RJ

Abstract

The periodontal pathogen Porphyromonas gingivalis employs a variety of mechanisms for the uptake of hemin and inorganic iron. Previous work demonstrated that hemin uptake in P. gingivalis may be controlled by LuxS-mediated signaling. In the present study, the expression of genes involved in hemin and iron uptake was determined in parent and luxS mutant strains by quantitative real-time reverse transcription-PCR. Compared to the parental strain, the luxS mutant showed reduced levels of transcription of genes coding for the TonB-linked hemin binding protein Tlr and the lysine-specific protease Kgp, which can degrade host heme-containing proteins. In contrast, there was up-regulation of the genes for another TonB-linked hemin binding protein, HmuR; a hemin binding lipoprotein, FetB; a Fe(2+) ion transport protein, FeoB1; and the iron storage protein ferritin. Differential expression of these genes in the luxS mutant was maximal in early-exponential phase, which corresponded with peak expression of luxS and AI-2 signal activity. Complementation of the luxS mutation with wild-type luxS in trans rescued expression of hmuR. Mutation of the GppX two-component signal transduction pathway caused an increase in expression of luxS along with tlr and lower levels of message for hmuR. Moreover, expression of hmuR was repressed, and expression of tlr stimulated, when the luxS mutant was incubated with AI-2 partially purified from the culture supernatant of wild-type cells. A phenotypic outcome of the altered expression of genes involved in hemin uptake was impairment of growth of the luxS mutant in hemin-depleted medium. The results demonstrate a role of LuxS/AI-2 in the regulation of hemin and iron acquisition pathways in P. gingivalis and reveal a novel control pathway for luxS expression.

MeSH Terms
Bacterial Proteins/biosynthesis,genetics,physiology Carbon-Sulfur Lyases Gene Expression Regulation, Bacterial Genetic Complementation Test Hemin/metabolism Histidine Kinase Homoserine/analogs & derivatives,physiology Iron/metabolism Lactones Mutation Porphyromonas gingivalis/genetics,metabolism Protein Kinases/genetics Signal Transduction
Chemicals
Bacterial Proteins Lactones N-octanoylhomoserine lactone Homoserine Hemin Iron Protein Kinases Histidine Kinase Carbon-Sulfur Lyases LuxS protein, Bacteria
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
James Chloe E
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
Hasegawa Yoshiaki
Park Yoonsuk
Yeung Vincent
Tribble Gena D
Kuboniwa Masae
Demuth Donald R
Lamont Richard J
References (82)
82 references, click to expand
  1. Chemical synthesis of (S)-4,5-dihydroxy-2,3-pentanedione, a bacterial signal molecule precursor, and validation of its activity in Salmonella typhimurium.
    J Biol Chem. 2005 May 20;280(20):19563-8 PMID: 15790567
  2. Short fimbriae of Porphyromonas gingivalis and their role in coadhesion with Streptococcus gordonii.
    Infect Immun. 2005 Jul;73(7):3983-9 PMID: 15972485
  3. A novel Porphyromonas gingivalis FeoB plays a role in manganese accumulation.
    J Biol Chem. 2005 Jul 29;280(30):28095-102 PMID: 15901729
  4. Construction and analysis of a Mannheimia haemolytica A1 luxS mutant.
    Vet Microbiol. 2005 Sep 30;110(1-2):53-66 PMID: 16061331
  5. Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15196-201 PMID: 10611361
  6. Regulation of competence for genetic transformation in Streptococcus pneumoniae: a link between quorum sensing and DNA processing genes.
    Res Microbiol. 2000 Jul-Aug;151(6):445-51 PMID: 10961457
  7. Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in sensing environmental conditions?
    Res Microbiol. 2000 Jul-Aug;151(6):457-63 PMID: 10961459
  8. Characterization and expression of HmuR, a TonB-dependent hemoglobin receptor of Porphyromonas gingivalis.
    J Bacteriol. 2000 Oct;182(20):5737-48 PMID: 11004172
  9. Characterization of a novel outer membrane hemin-binding protein of Porphyromonas gingivalis.
    J Bacteriol. 2000 Nov;182(22):6456-62 PMID: 11053391
  10. Emerging strategies in microbial haem capture.
    Mol Microbiol. 2001 Jan;39(1):1-11 PMID: 11123683
  11. A Porphyromonas gingivalis genetic locus encoding a heme transport system.
    Oral Microbiol Immunol. 2000 Dec;15(6):388-92 PMID: 11154437
  12. Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence.
    Mol Microbiol. 1993 Aug;9(4):773-86 PMID: 8231809
  13. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators.
    J Bacteriol. 1994 Jan;176(2):269-75 PMID: 8288518
  14. Binding and accumulation of hemin in Porphyromonas gingivalis are induced by hemin.
    Infect Immun. 1994 Jul;62(7):2885-92 PMID: 8005678
  15. The effect of growth rate and haemin on the virulence and proteolytic activity of Porphyromonas gingivalis W50.
    Microbiology. 1994 Apr;140 ( Pt 4):861-5 PMID: 8012602
  16. Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway.
    Mol Microbiol. 1994 Jul;13(2):273-86 PMID: 7984107
  17. Characterization of a Tn4351-generated hemin uptake mutant of Porphyromonas gingivalis: evidence for the coordinate regulation of virulence factors by hemin.
    Infect Immun. 1995 Jul;63(7):2459-66 PMID: 7790057
  18. Haemin binding as a factor in the virulence of Porphyromonas gingivalis.
    FEMS Microbiol Lett. 1996 Jul 15;141(1):65-70 PMID: 8764510
  19. Role of bacterial proteinases in matrix destruction and modulation of host responses.
    Periodontol 2000. 2000 Oct;24:153-92 PMID: 11276866
  20. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green I.
    Immunol Cell Biol. 2001 Jun;79(3):213-21 PMID: 11380673
  21. Signaling system in Porphyromonas gingivalis based on a LuxS protein.
    J Bacteriol. 2001 Jul;183(13):3903-9 PMID: 11395453
  22. The languages of bacteria.
    Genes Dev. 2001 Jun 15;15(12):1468-80 PMID: 11410527
  23. Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli O157:H7.
    J Bacteriol. 2001 Sep;183(17):5187-97 PMID: 11489873
  24. The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule.
    Mol Microbiol. 2001 Jul;41(2):463-76 PMID: 11489131
  25. Binding specificity of the Porphyromonas gingivalis heme and hemoglobin receptor HmuR, gingipain K, and gingipain R1 for heme, porphyrins, and metalloporphyrins.
    J Bacteriol. 2001 Oct;183(19):5599-608 PMID: 11544222
  26. Degradation of host heme proteins by lysine- and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis.
    J Bacteriol. 2001 Oct;183(19):5609-16 PMID: 11544223
  27. Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes.
    Mol Microbiol. 2001 Oct;42(1):145-57 PMID: 11679074
  28. Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing.
    Annu Rev Genet. 2001;35:439-68 PMID: 11700290
  29. Intra- and interspecies regulation of gene expression by Actinobacillus actinomycetemcomitans LuxS.
    Infect Immun. 2001 Dec;69(12):7625-34 PMID: 11705942
  30. The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.
    Mol Microbiol. 2001 Nov;42(3):777-93 PMID: 11722742
  31. Interactions of Porphyromonas gingivalis with oxyhaemoglobin and deoxyhaemoglobin.
    Biochem J. 2002 Feb 15;362(Pt 1):239-45 PMID: 11829761
  32. LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence.
    Microbiology. 2002 Mar;148(Pt 3):763-72 PMID: 11882711
  33. LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.
    Microbiology. 2002 Apr;148(Pt 4):909-22 PMID: 11932438
  34. Immunization with the RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis protects against periodontal bone loss in the rat periodontitis model.
    Infect Immun. 2002 May;70(5):2480-6 PMID: 11953385
  35. The luxS gene is involved in cell-cell signalling for toxin production in Clostridium perfringens.
    Mol Microbiol. 2002 Apr;44(1):171-9 PMID: 11967077
  36. pfs-dependent regulation of autoinducer 2 production in Salmonella enterica serovar Typhimurium.
    J Bacteriol. 2002 Jul;184(13):3450-6 PMID: 12057938
  37. Small talk. Cell-to-cell communication in bacteria.
    Cell. 2002 May 17;109(4):421-4 PMID: 12086599
  38. Communication among oral bacteria.
    Microbiol Mol Biol Rev. 2002 Sep;66(3):486-505, table of contents PMID: 12209001
  39. In or out: the invasiveness of oral bacteria.
    Periodontol 2000. 2002;30:61-9 PMID: 12236896
  40. Cell to cell communication by autoinducing peptides in gram-positive bacteria.
    Antonie Van Leeuwenhoek. 2002 Aug;81(1-4):233-43 PMID: 12448722
  41. LuxS-based signaling in Streptococcus gordonii: autoinducer 2 controls carbohydrate metabolism and biofilm formation with Porphyromonas gingivalis.
    J Bacteriol. 2003 Jan;185(1):274-84 PMID: 12486064
  42. luxS and arcB control aerobic growth of Actinobacillus actinomycetemcomitans under iron limitation.
    Infect Immun. 2003 Jan;71(1):298-308 PMID: 12496179
  43. Mutation of luxS affects biofilm formation in Streptococcus mutans.
    Infect Immun. 2003 Apr;71(4):1972-9 PMID: 12654815
  44. New bacterial species associated with chronic periodontitis.
    J Dent Res. 2003 May;82(5):338-44 PMID: 12709498
  45. LuxS quorum sensing: more than just a numbers game.
    Curr Opin Microbiol. 2003 Apr;6(2):191-7 PMID: 12732311
  46. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system.
    Mol Microbiol. 2003 Jun;48(6):1647-64 PMID: 12791145
  47. Gingipain RgpB is excreted as a proenzyme in the vimA-defective mutant Porphyromonas gingivalis FLL92.
    Infect Immun. 2003 Jul;71(7):3740-7 PMID: 12819055
  48. In vitro environmental regulation of Porphyromonas gingivalis growth and virulence.
    Oral Microbiol Immunol. 2003 Aug;18(4):226-33 PMID: 12823798
  49. Bacteria-host communication: the language of hormones.
    Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8951-6 PMID: 12847292
  50. Autoinducer 2 production by Streptococcus gordonii DL1 and the biofilm phenotype of a luxS mutant are influenced by nutritional conditions.
    J Bacteriol. 2003 Aug;185(16):4851-60 PMID: 12897005
  51. Quorum sensing controls biofilm formation in Vibrio cholerae.
    Mol Microbiol. 2003 Oct;50(1):101-4 PMID: 14507367
  52. A novel type of two-component regulatory system affecting gingipains in Porphyromonas gingivalis.
    Microbiol Immunol. 2003;47(11):849-58 PMID: 14638996
  53. Characterization of monospecies biofilm formation by Helicobacter pylori.
    J Bacteriol. 2004 May;186(10):3124-32 PMID: 15126474
  54. Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis.
    Infect Immun. 2004 Jul;72(7):3743-51 PMID: 15213114
  55. Growth phase regulation of flaA expression in Helicobacter pylori is luxS dependent.
    Infect Immun. 2004 Sep;72(9):5506-10 PMID: 15322055
  56. Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2.
    Mol Cell. 2004 Sep 10;15(5):677-87 PMID: 15350213
  57. Studies on transformation of Escherichia coli with plasmids.
    J Mol Biol. 1983 Jun 5;166(4):557-80 PMID: 6345791
  58. Hemin levels in culture medium of Porphyromonas (Bacteroides) gingivalis regulate both hemin binding and trypsinlike protease production.
    Infect Immun. 1990 Dec;58(12):4016-9 PMID: 2254026
  59. The microflora of periodontal sites showing active destructive progression.
    J Clin Periodontol. 1991 Nov;18(10):729-39 PMID: 1752997
  60. Haemin-restriction influences haemin-binding, haemagglutination and protease activity of cells and extracellular membrane vesicles of Porphyromonas gingivalis W50.
    FEMS Microbiol Lett. 1991 Dec 15;69(1):63-7 PMID: 1664402
  61. Hemin uptake in Porphyromonas gingivalis: Omp26 is a hemin-binding surface protein.
    J Bacteriol. 1993 Nov;175(22):7413-20 PMID: 8226688
  62. Isolation and characterization of a hemin-binding cell envelope protein from Porphyromonas gingivalis.
    Microb Pathog. 1996 Jul;21(1):65-70 PMID: 8827708
  63. Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators.
    Annu Rev Microbiol. 1996;50:727-51 PMID: 8905097
  64. Effect of host responses on the pathogenicity of strains of Porphyromonas gingivalis.
    Oral Microbiol Immunol. 1996 Oct;11(5):309-18 PMID: 9028256
  65. Isolation and characterization of a hemin-regulated gene, hemR, from Porphyromonas gingivalis.
    J Bacteriol. 1997 Mar;179(6):1898-908 PMID: 9068634
  66. The prpR1 and prR2 arginine-specific protease genes of Porphyromonas gingivalis W50 produce five biochemically distinct enzymes.
    Mol Microbiol. 1997 Mar;23(5):955-65 PMID: 9076732
  67. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi.
    J Bacteriol. 1997 Jun;179(12):4043-5 PMID: 9190823
  68. The Tla protein of Porphyromonas gingivalis W50: a homolog of the RI protease precursor (PrpRI) is an outer membrane receptor required for growth on low levels of hemin.
    J Bacteriol. 1997 Aug;179(15):4778-88 PMID: 9244265
  69. Cell-cell communication in gram-positive bacteria.
    Annu Rev Microbiol. 1997;51:527-64 PMID: 9343359
  70. The involvement of cell-to-cell signals in the development of a bacterial biofilm.
    Science. 1998 Apr 10;280(5361):295-8 PMID: 9535661
  71. Quorum sensing in Escherichia coli and Salmonella typhimurium.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7046-50 PMID: 9618536
  72. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis.
    Microbiol Mol Biol Rev. 1998 Dec;62(4):1244-63 PMID: 9841671
  73. Sequence and function of LuxU: a two-component phosphorelay protein that regulates quorum sensing in Vibrio harveyi.
    J Bacteriol. 1999 Feb;181(3):899-906 PMID: 9922254
  74. Regulation of autoinducer production in Salmonella typhimurium.
    Mol Microbiol. 1999 Jan;31(2):585-95 PMID: 10027975
  75. A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi.
    Mol Microbiol. 1999 Jan;31(2):665-77 PMID: 10027982
  76. Transposition of the endogenous insertion sequence element IS1126 modulates gingipain expression in Porphyromonas gingivalis.
    Infect Immun. 1999 Oct;67(10):5012-20 PMID: 10496872
  77. Interspecies communication in Streptococcus gordonii-Veillonella atypica biofilms: signaling in flow conditions requires juxtaposition.
    Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16917-22 PMID: 15546975
  78. Iron and heme utilization in Porphyromonas gingivalis.
    FEMS Microbiol Rev. 2005 Jan;29(1):119-44 PMID: 15652979
  79. Quorum sensing in Clostridium difficile: analysis of a luxS-type signalling system.
    J Med Microbiol. 2005 Feb;54(Pt 2):119-27 PMID: 15673504
  80. Altered gingipain maturation in vimA- and vimE-defective isogenic mutants of Porphyromonas gingivalis.
    Infect Immun. 2005 Mar;73(3):1357-66 PMID: 15731033
  81. Making 'sense' of metabolism: autoinducer-2, LuxS and pathogenic bacteria.
    Nat Rev Microbiol. 2005 May;3(5):383-96 PMID: 15864263
  82. LuxS-based signaling affects Streptococcus mutans biofilm formation.
    Appl Environ Microbiol. 2005 May;71(5):2372-80 PMID: 15870324
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.01768-05
Published
2006-07-00
Pages
3834-44
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1489751
Subset
IM
Grants
NIDCR NIH HHS · R01 DE014605 · United States
NIDCR NIH HHS · R01 DE14604 · United States
External Links
PubMed source DOI: 10.1128/IAI.01768-05 PMC Full Text View journal details
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