Two-component signal transduction as potential drug targets in pathogenic bacteria

Current Opinion in Microbiology

Volumn 13, Issue 2, 2010, Pages 232-239

  Gotoh, Yasuhiro ^a   Eguchi, Yoko ^a   Watanabe, Takafumi ^a   Okamoto, Sho ^a   Doi, Akihiro ^a   Utsumi, Ryutaro ^a  

^a KINKI UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; PROTEIN HISTIDINE KINASE; VIRULENCE FACTOR;

ANTIBIOTIC RESISTANCE; BACTERIAL VIRULENCE; CELL GROWTH; DRUG TARGETING; GENE CLUSTER; NONHUMAN; PROTEIN DOMAIN; QUORUM SENSING; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIAL INFECTIONS; BACTERIAL PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; SIGNAL TRANSDUCTION; VIRULENCE;

EID: 77949916499     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mib.2010.01.008     Document Type: Review

References (67)

1. Gao R., and Stock A.M. Biological insights from structures of two-component proteins. Annu Rev Microbiol 63 (2009) 133-154
2. Eguchi Y., and Utsumi R. Introduction to bacterial signal transduction networks. Adv Exp Med Biol 631 (2008) 1-6
3. Mitrophanov A.Y., and Groisman E.A. Signal integration in bacterial two-component regulatory systems. Genes Dev 22 (2008) 2601-2611
4. Dubrac S., and Msadek T. Tearing down the wall: peptidoglycan metabolism and the WalK/WalR (YycG/YycF) essential two-component system. Adv Exp Med Biol 631 (2008) 214-228
5. Watanabe T., Okada A., Gotoh Y., and Utsumi R. Inhibitors targeting two-component signal transduction. Adv Exp Med Biol 631 (2008) 229-236
6. Okada A, Igarashi M, Okajima T, Kinoshita N, Umekita M, Sawa R, Inouye K, Watanabe T, Doi A, Martin A, et al.: Walkmycin B targets WalK (YycG), a histidine kinase essential for bacterial cell growth. J Antibiot, in press. Walkmycin B is the first antibiotic targeting WalK histidine kinase.
7. Gotoh Y, Doi A, Furuta E, Dubrac S, Ishizaki Y, Okada M, Igarashi M, Misawa N, Yoshikawa H, Okajima T, et al.: Novel antibacterial compounds specifically targeting the essential WalR response regulator. J Antibiot in press. Walrycins are the first inhibitors targeting WalR response regulator.
8. Cegelski L., Marshall G.R., Eldridge G.R., and Hultgren S.J. The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 6 (2008) 17-27
9. Dong Y.H., Wang L.H., Xu J.L., Zhang H.B., Zhang X.F., and Zhang L.H. Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411 (2001) 813-817
10. Rasko D.A., Moreira C.G., Li de R., Reading N.C., Ritchie J.M., Waldor M.K., Williams N., Taussig R., Wei S., Roth M., et al. Targeting QseC signaling and virulence for antibiotic development. Science 321 (2008) 1078-1080. Inhibitor (LED209) of QseC histidine kinase is not toxic and dose not inhibit pathogen growth, but markedly inhibits the virulence of several pathogens in vitro and in vivo in animals.
11. Chauhan N., and Calderone R. Two-component signal transduction proteins as potential drug targets in medically important fungi. Infect Immun 76 (2008) 4795-4803
12. Martin P.K., Li T., Sun D., Biek D.P., and Schmid M.B. Role in cell permeability of an essential two-component system in Staphylococcus aureus. J Bacteriol 181 (1999) 3666-3673
13. Lange R., Wagner C., de Saizieu A., Flint N., Molnos J., Stieger M., Caspers P., Kamber M., Keck W., and Amrein K.E. Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae. Gene 237 (1999) 223-234
14. Senadheera M.D., Guggenheim B., Spatafora G.A., Huang Y.C., Choi J., Hung D.C., Treglown J.S., Goodman S.D., Ellen R.P., and Cvitkovitch D.G. A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J Bacteriol 187 (2005) 4064-4076
15. Liu M., Hanks T.S., Zhang J., McClure M.J., Siemsen D.W., Elser J.L., Quinn M.T., and Lei B. Defects in ex vivo and in vivo growth and sensitivity to osmotic stress of group A Streptococcus caused by interruption of response regulator gene vicR. Microbiology 152 (2006) 967-978
16. Qin Z., Zhang J., Xu B., Chen L., Wu Y., Yang X., Shen X., Molin S., Danchin A., Jiang H., et al. Structure-based discovery of inhibitors of the YycG histidine kinase: new chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol 6 (2006) 96
17. Kallipolitis B.H., and Ingmer H. Listeria monocytogenes response regulators important for stress tolerance and pathogenesis. FEMS Microbiol Lett 204 (2001) 111-115
18. Hancock L., and Perego M. Two-component signal transduction in Enterococcus faecalis. J Bacteriol 184 (2002) 5819-5825
19. Sun J., Zheng L., Landwehr C., Yang J., and Ji Y. Identification of a novel essential two-component signal transduction system, YhcSR, in Staphylococcus aureus. J Bacteriol 187 (2005) 7876-7880
20. Beier D., and Frank R. Molecular characterization of two-component systems of Helicobacter pylori. J Bacteriol 182 (2000) 2068-2076
21. Zahrt T.C., and Deretic V. An essential two-component signal transduction system in Mycobacterium tuberculosis. J Bacteriol 182 (2000) 3832-3838
22. Dubrac S., Bisicchia P., Devine K.M., and Msadek T. A matter of life and death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction pathway. Mol Microbiol 70 (2008) 1307-1322. Review of WalK/WalR signal transduction pathways of Gram-positive pathogens.
23. Dubrac S., Boneca I.G., Poupel O., and Msadek T. New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J Bacteriol 189 (2007) 8257-8269
24. Okada A., Gotoh Y., Watanabe T., Furuta E., Yamamoto K., and Utsumi R. Targeting two-component signal transduction: a novel drug discovery system. Methods Enzymol 422 (2007) 386-395
25. Gooderham W.J., and Hancock R.E. Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiol Rev 33 (2009) 279-294
26. Sperandio V., Mellies J.L., Nguyen W., Shin S., and Kaper J.B. 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 96 (1999) 15196-15201
27. Sperandio V., Torres A.G., Jarvis B., Nataro J.P., and Kaper J.B. Bacteria-host communication: the language of hormones. Proc Natl Acad Sci U S A 100 (2003) 8951-8956
28. Njoroge J., and Sperandio V. Jamming bacterial communication: New approaches for the treatment of infectious diseases. EMBO Mol Med 1 (2009) 201-210. Inhibition of quorum sensing via TCSs (AgrC/AgrA, QseC/QseB) is important for treatment of infectious diseases.
29. George E.A., and Muir T.W. Molecular mechanisms of agr quorum sensing in virulent staphylococci. ChemBioChem 8 (2007) 847-855
30. Lina G., Jarraud S., Ji G., Greenland T., Pedraza A., Etienne J., Novick R.P., and Vandenesch F. Transmembrane topology and histidine protein kinase activity of AgrC, the agr signal receptor in Staphylococcus aureus. Mol Microbiol 28 (1998) 655-662
31. Peterson M.M., Mack J.L., Hall P.R., Alsup A.A., Alexander S.M., Sully E.K., Sawires Y.S., Cheung A.L., Otto M., and Gresham H.D. Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection. Cell Host Microbe 4 (2008) 555-566
32. Lyon G.L., Mayville P., Muir T.W., and Novick R.P. Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase, AgrC. Proc Natl Acad Sci U S A 97 (2000) 13330-13335
33. Geisinger E., Muir T.W., and Novick R.P. agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proc Natl Acad Sci U S A 106 (2009) 1216-1221
34. Balaban N., Goldkorn T., Gov Y., Hirshberg M., Koyfman N., Matthews H.R., Nhan R.T., Singh B., and Uziel O. Regulation of Staphylococcus aureus pathogenesis via target of RNA III-activating protein (TRAP). J Biol Chem 276 (2001) 2658-2667
35. Shaw L.N., Jonsson I.M., Singh V.K., Tarkowski A., and Stewart G.C. Inactivation of traP has no effect on the agr quorum-sensing system or virulence of Staphylococcus aureus. Infect Immun 75 (2007) 4519-4527
36. Tsang L.H., Daily S.T., Weiss E.C., and Smeltzer M.S. Mutation of traP in Staphylococcus aureus has no impact on expression of agr or biofilm formation. Infect Immun 75 (2007) 4528-4533
37. Adhikari R.P., Arvidson S., and Novick R.P. A nonsense mutation in agrA accounts for the defect in agr expression and the avirulence of Staphylococcus aureus 8325-4 traP::kan. Infect Immun 75 (2007) 4534-4540
38. Gov Y., Borovok I., Korem M., Singh V.K., Jayaswal R.K., Wilkinson B.J., Rich S.M., and Balaban N. Quorum sensing in staphylococci is regulated via phosphorylation of three conserved histidine residues. J Biol Chem 279 (2004) 14665-14672
39. Kiran M.D., Adikesavan N.V., Cirioni O., Giacometti A., Silvestri C., Scalise G., Ghiselli R., Saba V., Orlando F., Shoham M., and Balaban N. Discovery of a quorum-sensing inhibitor of drug-resistant Staphylococcal infections by structure-based virtual screening. Mol Pharmacol 73 (2008) 1578-1586
40. Hancock L.E., and Gilmore M.S. Pathogenicity of enterococci. In: Fischetti V.A., Novick R.P., Ferretti J.J., Portnoy D.A., and Rood J.I. (Eds). Gram-Positive Pathogens (2000), ASM Press
41. Rice L.B. Emergence of vancomycin-resistant enterococci. Emerg Infect Dis 7 (2001) 183-187
42. Qin X., Singh K.V., Weinstock G.M., and Murray B.E. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect Immun 68 (2000) 2579-2586
43. Nakayama J., Cao Y., Horii T., Sakuda S., Akkermans A.D., de Vos W.M., and Nagasawa H. Gelatinase biosynthesis-activating pheromone: a peptide lactone that mediates a quorum sensing in Enterococcus faecalis. Mol Microbiol 41 (2001) 145-154
44. Nakayama J., Tanaka E., Kariyama R., Nagata K., Nishiguchi K., Mitsuhata R., Uemura Y., Tanokura M., Kumon H., and Sonomoto K. Siamycin attenuates fsr quorum sensing mediated by a gelatinase biosynthesis-activating pheromone in Enterococcus faecalis. J Bacteriol 189 (2007) 1358-1365
45. Goodman A.L., Merighi M., Hyodo M., Ventre I., Filloux A., and Lory S. Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen. Genes Dev 23 (2009) 249-259. Virulence of Pseudomas aeruginosa is determined by direct interaction between sensor kinases, RetS and GacS.
46. Lapouge K., Schubert M., Allain F.H., and Haas D. Gac/Rsm signal transduction pathway of gamma-proteobacteria: from RNA recognition to regulation of social behaviour. Mol Microbiol 67 (2008) 241-253
47. Hyytiainen H., Montesano M., and Palva E.T. Global regulators ExpA (GacA) and KdgR modulate extracellular enzyme gene expression through the RsmA-rsmB system in Erwinia carotovora subsp. carotovora. Mol Plant Microbe Interact 14 (2001) 931-938
48. Miller S.I., and Mekalanos J.J. Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J Bacteriol 172 (1990) 2485-2490
49. Fields P.I., Groisman E.A., and Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science 243 (1989) 1059-1062
50. Miller S.I., Kukral A.M., and Mekalanos J.J. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 86 (1989) 5054-5058
51. Dutta R., and Inouye M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci 25 (2000) 24-28
52. Guarnieri M.T., Zhang L., Shen J., and Zhao R. The Hsp90 inhibitor radicicol interacts with the ATP-binding pocket of bacterial sensor kinase PhoQ. J Mol Biol 379 (2008) 82-93
53. Flego D., Marits R., Eriksson A.R., Koiv V., Karlsson M.B., Heikinheimo R., and Palva E.T. A two-component regulatory system, pehR-pehS, controls endopolygalacturonase production and virulence in the plant pathogen Erwinia carotovora subsp. carotovora. Mol Plant Microbe Interact 13 (2000) 447-455
54. Penaloza-Vazquez A., and Bender C.L. Characterization of CorR, a transcriptional activator which is required for biosynthesis of the phytotoxin coronatine. J Bacteriol 180 (1998) 6252-6259
55. Wang L., Bender C.L., and Ullrich M.S. The transcriptional activator CorR is involved in biosynthesis of the phytotoxin coronatine and binds to the cmaABT promoter region in a temperature-dependent manner. Mol Gen Genet 262 (1999) 250-260
56. Sreedharan A., Penaloza-Vazquez A., Kunkel B.N., and Bender C.L. CorR regulates multiple components of virulence in Pseudomonas syringae pv. tomato DC3000. Mol Plant-Microbe Interact 19 (2006) 768-779
57. Buttner D., and He S.Y. Type III protein secretion in plant pathogenic bacteria. Plant Physiol 150 (2009) 1656-1664
58. Bogdanove A.J., Bauer D.W., and Beer S.V. Erwinia amylovora secretes DspE, a pathogenicity factor and functional AvrE homolog, through the Hrp (type III secretion) pathway. J Bacteriol 180 (1998) 2244-2247
59. Kim J.F., and Beer S.V. HrpW of Erwinia amylovora, a new harpin that contains a domain homologous to pectate lyases of a distinct class. J Bacteriol 180 (1998) 5203-5210
60. Kim J.F., Wei Z.M., and Beer S.V. The hrpA and hrpC operons of Erwinia amylovora encode components of a type III pathway that secretes harpin. J Bacteriol 179 (1997) 1690-1697
61. Wei Z., Kim J.F., and Beer S.V. Regulation of hrp genes and type III protein secretion in Erwinia amylovora by HrpX/HrpY, a novel two-component system, and HrpS. Mol Plant Microbe Interact 13 (2000) 1251-1262
62. Wei Z.M., and Beer S.V. hrpL activates Erwinia amylovora hrp gene transcription and is a member of the ECF subfamily of sigma factors. J Bacteriol 177 (1995) 6201-6210
63. Li Y., Peng Q., Selimi D., Wang Q., Charkowski A.O., Chen X., and Yang C.H. The plant phenolic compound p-coumaric acid represses gene expression in the Dickeya dadantii type III secretion system. Appl Environ Microbiol 75 (2009) 1223-1228
64. Hilliard J.J., Goldschmidt R.M., Licata L., Baum E.Z., and Bush K. Mutiple mechanisms of action for inhibitors of histidine protein kinases from bacterial two-component systems. Antimicrob Agents Chemother 43 (1999) 1693-1699
65. Stephenson K., and Hoch J.A. Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms. Curr Med Chem 11 (2004) 765-773
66. Dietz P., Gerlach G., and Beier D. Identification of target genes regulated by the two-component system HP166-HP165 of Helicobacter pylori. J Bacteriol 184 (2002) 350-362
67. Fol M., Chauhan A., Nair N.K., Maloney E., Moomey M., Jagannath C., Madiraju M.V., and Rajagopalan M. Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator. Mol Microbiol 60 (2006) 643-657