Two-Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis

Yossef Av-Gay; Vojo Deretic

doi:10.1128/9781555817657.ch22

Chapter 22 : Two-Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Division of Infectious Diseases, University of British Columbia, Vancouver, BC, Canada V5Z-3J5; 2: University of New Mexico Medical School, Albuquerque, NM 87131

Content Type: Monograph

Publication Year: 2005

Category: Bacterial Pathogenesis; Clinical Microbiology

Book DOI: 10.1128/9781555817657

Chapter DOI: 10.1128/9781555817657.ch22

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Two-Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap22-2.gif

Abstract:

This chapter covers two types of regulatory signal transduction elements in Mycobacterium tuberculosis: (i) histidine protein kinase response regulators, referred to as two-component systems, and (ii) eucaryotic-type Ser/Thr protein kinases (STPKs). The chapter is divided into two parts, covering the two types of phosphotransfer signaling systems individually. The prototypical two-component systems consist of a histidine protein kinase (often functioning as an environmental sensor), which, as a manifestation of signal transduction, phosphorylates an aspartate residue on its cognate response regulator (a transcriptional regulator or a regulator of other proteins). The observations that inactivation of five different two-component systems increases the ability of M. tuberculosis to kill the murine host or enhances the growth of the mutant strains in mice or macrophages may reflect evolutionary adaptations of M. tuberculosis important for propagation and infectious cycle of the pathogen. Protein phosphorylation is carried out by specific protein kinases and is coupled to dephosphorylation reactions carried out by protein phosphatases. The eukaryotic protein kinases and phosphatases form the backbone of this signal transduction pathway. M. tuberculosis encodes and expresses at least eight eukaryotic-like protein kinases, and six proteins can be phosphorylated in vitro, suggesting the presence of functional kinases in M. tuberculosis. Interference with the normal immune response of the host during mycobacterial infection could be mediated by disabling host signaling pathways.

Citation: Av-Gay Y, Deretic V. 2005. Two-Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis, p 359-367. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch22

Key Concept Ranking

Two-Component Signal Transduction Systems: 0.4806253
Bacterial Proteins: 0.40737817

0.4806253

Highlighted Text: Show | Hide

Full text loading...

References

/content/book/10.1128/9781555817657.chap22

1. Av-Gay, Y.,, and J. E. Davies. 1997. Components of eukaryotic-like signaling pathways in Mycobacterium tuberculosis. Microb. and Comp. Genomics 2: 63– 73.

2. Av-Gay, Y.,, and M. Everett. 2000. The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Trends Microbiol. 8: 238– 244.

3. Av-Gay, Y.,, S. Jamil,, and S. J. Drews. 1999. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Infect. Immun. 67: 5676– 5682.

4. Behr, M. A.,, M. A. Wilson,, W. P. Gill,, H. Salamon,, G. K. Schoolnik,, S. Rane,, and P. M. Small. 1999. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284: 1520– 1523.

5. Belanger, A. E.,, G. S. Besra,, M. E. Ford,, K. Mikusova,, J. T. Belisle,, P. J. Brennan,, and J. M. Inamine. 1996. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in the cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl. Acad. Sci. USA 93: 11919–11924..

6. Chaba, R.,, M. Raje,, and P. K. Chakraborti. 2002. Evidence that a eukaryotic-type serine/threonine protein kinase from Mycobacterium tuberculosis regulates morphological changes associated with cell division. Eur. J. Biochem. 269: 1078– 1085.

7. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry III,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, A. Krogh,, J. McLean,, S. Moule,, L. Murphy,, K. Oliver,, J. Osborne,, M. A. Quail,, M.-A. Rajandream,, J. Rogers,, S. Rutter,, K. Seeger,, J. Skelton,, R. Squares,, S. Squares,, J. E. Sulston,, K. Taylor,, S. Whitehead,, and B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537– 544.

8. Cole, S. T.,, K. Eiglmeier,, J. Parkhill,, K. D. James,, N. R. Thomson,, P. R. Wheeler,, N. Honore,, T. Garnier,, C. Churcher,, D. Harris,, K. Mungall,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. M. Davies,, K. Devlin,, S. Duthoy,, T. Feltwell,, A. Fraser,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, C. Lacroix,, J. Maclean,, S. Moule,, L. Murphy,, K. Oliver,, M. A. Quail,, M.-A. Rajandream,, K. M. Rutherford,, S. Rutter,, K. Seeger,, S. Simon,, M. Simmonds,, M. Skelton,, R. Squares,, S. Squares,, K. Stevens,, K. Taylor,, S. Whitehead,, J. R. Woodward,, and B. G. Barrell. 2001. Massive gene decay in the leprosy bacillus. Nature 409: 1007– 1011.

9. Cowley, S.,, and Y. Av-Gay. 2001. Monitoring promoter activity and protein localization in Mycobacterium spp. Using green fluorescent protein. Gene 264: 225– 231.

9a.. Cowley, S.,, S. J. Drews,, O. Tang,, S. Jamil,, M. Ko,, and Y. Av- Gay. 2000. Investigations of the eukaryotic serine/threonine kinases of M. tuberculosis. Tubercle Lung Dis. 80: 96.

10. Cowley, S. C.,, R. Babakaiff,, and Y. Av-Gay. 2002. Expression and localization of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Res. Microbiol. 153: 233– 241.

11. Cozier, G. E.,, I. G. Giles,, and C. Anthony. 1995. The structure of the quinoprotein alcohol dehydrogenase of Acetobacter aceti modelled on that of methanol dehydrogenase from Methylobacterium extorquens. Biochem. J. 308: 375– 379.

12. Curcic, R.,, S. Dhandayuthapani,, and V. Deretic. 1994. Gene expression in mycobacteria: transcriptional fusions based on xylE and analysis of the promoter region of the response regulator mtrA from Mycobacterium tuberculosis. Mol. Microbiol. 13: 1057– 1064.

13. Dasgupta, N.,, V. Kapur,, K. K. Singh,, T. K. Das,, S. Sachdeva,, K. Jyothisri,, and J. S. Tyagi. 2000. Characterization of a twocomponent system, devR-devS, of Mycobacterium tuberculosis. Tubercle Lung Dis. 80: 141– 159.

14. DeMaio, J.,, Y. Zhang,, C. Ko,, D. B. Young,, and W. R. Bishai. 1996. A stationary-phase stress-response sigma factor from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 93: 2790– 2794.

15. Drews, S. J.,, F. Hung,, and Y. Av-Gay. 2001. A protein kinase inhibitor as an antimycobacterial agent. FEMS Microbiol. Lett. 205: 369– 374.

16. Ewann, F.,, M. Jackson,, K. Pethe,, A. Cooper,, N. Mielcarek,, D. Ensergueix,, B. Gicquel,, C. Locht,, and P. Supply. 2002. Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis Infect. Immun. 70: 2256– 2263.

17. Fratti, R. A.,, J. M. Backer,, J. Gruenberg,, S. Corvera,, and V. Deretic. 2001. Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J. Cell Biol. 154: 631– 644.

18. Fratti, R. A.,, J. Chua,, I. Vergne,, and V. Deretic. 2003. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Natl. Acad. Sci USA 100: 5437– 5442.

19. Graham, J. E.,, and J. E. Clark-Curtiss. 1999. Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc. Natl. Acad. Sci. USA 96: 11554– 11559.

20. Hakansson, S.,, E. E. Galyov,, R. Rosqvist,, and H. Wolf-Watz. 1996. The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targetted to the inner surface of the HeLa cell plasma membrane. Mol. Microbiol. 20: 593– 603.

21. Hanks, S. K.,, and A. M. Quinn. 1991. Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. Methods Enzymol. 200: 38– 62.

22. Hanlon, W. A.,, M. Inouye,, and S. Inouye. 1997. Pkn9, a Ser/Thr protein kinase involved in the development of Myxococcus xanthus. Mol. Microbiol. 23: 459– 471.

23. Haydel, S. E.,, W. H. Benjamin, Jr.,, N. E. Dunlap,, and J. E. Clark-Curtiss. 2002. Expression, autoregulation, and DNA binding properties of the Mycobacterium tuberculosis TrcR response regulator. J. Bacteriol. 184: 2192– 2203.

24. Haydel, S. E.,, N. E. Dunlap,, and W. H. Benjamin, Jr. 1999. In vitro evidence of two-component system phosphorylation between the Mycobacterium tuberculosis TrcR/TrcS proteins. Microb. Pathog. 26: 195– 206.

25. Henriques, A. O.,, P. Glaser,, P. J. Piggot,, and C. P. Moran, Jr. 1998. Control of cell shape and elongation by the rodA gene in Bacillus subtilis. Mol. Microbiol. 28: 235– 247.

26. Himpens, S.,, C. Locht,, and P. Supply. 2000. Molecular characterization of the mycobacterial SenX3-RegX3 two-component system: evidence for autoregulation. Microbiology 146: 3091– 3098.

26a.. Karlsgot Hestrik, A. L.,, Z. Hmama,, and Y. Av-Gay. 2003. Kinome analysis of host response to mycobacterial infection. Infect. Immun. 71: 5514– 5522.

27. Kennelly, P. J.,, and M. Potts. 1996. Fancy meeting you here! A fresh look at “prokaryotic” protein phosphorylation. J. Bacteriol. 178: 4759– 4764.

28. Koul, A.,, A. Choidas,, A. K. Tyagi,, K. Drlica,, Y. Singh,, and A. Ullrich. 2001. Serine/Threonine protein kinases PknF and PknG of Mycobacterium tuberculosis: characterization and localization. Microbiology 147: 2307– 2314.

29. Ludwiczak, P.,, M. Gilleron,, Y. Bordat,, C. Martin,, B. Gicquel,, and G. Puzo. 2002. Mycobacterium tuberculosis phoP mutant: lipoarabinomannan molecular structure. Microbiology 148: 3029– 3037.

30. Matsumoto, A.,, S. K. Hong,, H. Ishizuka,, S. Horinouchi,, and T. Beppu. 1994. Phosphorylation of the AfsR protein involved in secondary metabolism in Streptomyces species by a eukaryotic-type protein kinase. Gene 146: 47– 56.

31. Mayuri, G. Bagchi, T. K. Das, and J. S. Tyagi. 2002. Molecular analysis of the dormancy response in Mycobacterium smegmatis: expression analysis of genes encoding the DevRDevS two-component system, Rv3134c and chaperone alphacrystallin homologues. FEMS Microbiol. Lett. 211: 231– 237.

32. McAdam, R. A.,, S. Quan,, D. A. Smith,, S. Bardarov,, J. C. Betts,, F. C. Cook,, E. U. Hooker,, A. P. Lewis,, P. Woollard,, M. J. Everett,, P. T. Lukey,, G. J. Bancroft,, W. R. J. Jacobs,, and K. Duncan. 2002. Characterization of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 ORFs and mutants with altered virulence. Microbiology 148: 2975– 2986.

33. Nadvornik, R.,, T. Vomastek,, J. Janecek,, Z. Technikova,, and P. Branny. 1999. Pkg2, a novel transmembrane protein Ser/Thr kinase of Streptomyces granaticolor. J. Bacteriol. 181: 15– 23.

34. Parish, T.,, D. A. Smith,, S. Kendall,, N. Casali,, G. J. Bancroft,, and N. G. Stoker. 2003. Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis. Infect. Immun. 71: 1134– 1140.

35. Peirs, P.,, L. De Wit,, M. Braibant,, K. Huygen,, and J. Content. 1997. A serine/threonine protein kinase from Mycobacterium tuberculosis. Eur. J. Biochem. 244: 604– 612.

36. Peirs, P.,, B. Parmentier,, L. De Wit,, and J. Content. 2000. The Mycobacterium bovis homologous protein of the Mycobacterium tuberculosis serine/threonine protein kinase Mbk (PknD) is truncated. FEMS Microbiol. Lett. 188: 135– 139.

37. Perez, E.,, S. Samper,, Y. Bordas,, C. Guilhot,, B. Gicquel,, and C. Martin. 2001. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 41: 179– 187.

38. Ponting, C. P.,, C. Phillips,, K. E. Davies,, and D. J. Blake. 1997. PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays 19: 469– 479.

39. Ronson, C. W.,, B. T. Nixon,, and F. M. Ausubel. 1987. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell 49: 579– 581.

40. Russell, D. G.,, H. C. Mwandumba,, and E. E. Rhoades. 2002. Mycobacterium and the coat of many lipids. J. Cell Biol. 158: 421– 426.

41. Saini, D. K.,, N. Pant,, T. K. Das,, and J. S. Tyagi. 2002. Cloning, overexpression, purification, and matrix-assisted refolding of DevS (Rv 3132c) histidine protein kinase of Mycobacterium tuberculosis. Protein Expression Purif. 25: 203– 208.

42. Sherman, D. R.,, M. Voskuil,, D. Schnappinger,, R. Liao,, M. I. Harrell,, and G. K. Schoolnik. 2001. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha-crystallin. Proc. Natl. Acad. Sci. USA 98: 7534– 7539.

43. Signoretto, C.,, F. Di Stefano,, and P. Canapari. 1996. Modified peptidoglycan chemical composition in shape-altered Escherichia coli. Microbiology 142: 1919– 1926.

44. Sikorski, R. S.,, M. S. Boguski,, M. Goebl,, and P. Hieter. 1990. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA sythesis. Cell 60: 307– 317.

45. Singh, K. K.,, X. Zhang,, A. S. Patibandla,, P. Chien, Jr.,, and S. Laal. 2001. Antigens of Mycobacterium tuberculosis expressed during preclinical tuberculosis: serological immunodominance of proteins with repetitive amino acid sequences. Infect. Immun. 69: 4185– 4191.

46. Springer, T. A. 1998. An extracellular beta-propeller module predicted in lipprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components. J. Mol. Biol. 283: 837– 862.

47. Stock, J. B.,, A. J. Ninfa,, and A. M. Stock. 1989. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol. Rev. 53: 450– 490.

48. Trach, K. A.,, J. W. Chapman,, P. J. Piggot,, and J. A. Hoch. 1985. Deduced product of the stage 0 sporulation gene spo0F shares homology with the Spo0A, OmpR, and SfrA proteins. Proc. Natl. Acad. Sci. USA 82: 7260– 7264.

49. Udo, H.,, M. Inouye,, and S. Inouye. 1997. Biochemical characterization of Pkn2, a protein Ser/Thr kinase from Myxococcus xanthus, a Gram-negative developmental bacterium. FEBS Lett. 400: 188– 192.

50. Urabe, H.,, and H. Ogawara. 1995. Cloning, sequencing, and expression of serine/threonine kinase-encoding genes from Streptomyces coelicolor A3(2). Gene 153: 99– 104.

51. Via, L. E.,, R. Curcic,, M. H. Mudd,, S. Dhandayuthapani,, R. J. Ulmer,, and V. Deretic. 1996. Elements of signal transduction and Mycobacterium tuberculosis: in vitro phosphorylation and in vivo expression of the response regulator MtrA. J. Bacteriol. 178: 3314– 3321.

52. Walderhaug, M. O.,, J. W. Polarek,, P. Voelkner,, J. M. Daniel,, J. E. Hesse,, K. Altendorf,, and W. Epstein. 1992. KdpD and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators. J. Bacteriol. 174: 2152– 2159.

53. Wang, J.,, C. Li,, H. Yang,, A. Mushegian,, and S. Jin. 1998. A novel serine/threonine protein kinase homologue of Pseudomonas aeruginosa is specifically inducible within the host infection site and is required for full virulence in neutropenic mice. J. Bacteriol. 180: 6764– 6768.

54. Wolanin, P. M.,, P. A. Thomason,, and J. B. Stock. 2002. Histidine protein kinases: key signal transducers outside the animal kingdom. Genome Biol. 3: REVIEWS3013.

55. Yates, C.,, R. D. Finn,, and A. Bateman. 2002. The PASTA domain: a beta-lactam-binding domain. Trends Biochem. Sci. 27: 438.

56. Young, T. A.,, B. Delagoutte,, J. A. Endrizzi,, A. M. Falick,, and T. Alber. 2003. Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat. Struct. Biol. 10: 168– 174.

57. Zahrt, T. C.,, and V. Deretic. 2000. An essential two-component signal transduction system in Mycobacterium tuberculosis. J Bacteriol. 182: 3832– 3838.

58. Zahrt, T. C.,, and V. Deretic. 2001. Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc. Natl. Acad. Sci. USA 98: 12706– 12711.

59. Zhang, C. C. 1996. Bacterial signalling involving eukaryotictype protein kinases. Mol. Microbiol. 20: 9– 15

60. Zhang, C. C.,, A. Friry,, and L. Peng. 1998. Molecular and genetic analysis of two closely linked genes that encode, respectively, a protein phosphatase 1/2A/2B homolog and a protein kinases homolog in the cyanobacterium Anabaena sp. Strain PCC 7120. J. Bacteriol. 180: 2616– 2622.

61. Zhang, C. C.,, and L. Libs. 1998. Cloning and characterisation of the pknD gene encoding an eukaryotic-type protein kinase in the cyanobacterium Anabaena sp. PCC7120. Mol. Gen. Genet. 258: 26– 33.

Tables

Two-Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817657.chap22-1,webId=/content/author/10.1128/9781555817657.chap22-1,properties={foaf_givenname=Yossef, foaf_name=Yossef Av-Gay, foaf_surname=Av-Gay, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817657.chap22-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817657.chap22-2,webId=/content/author/10.1128/9781555817657.chap22-2,properties={foaf_givenname=Vojo, foaf_name=Vojo Deretic, foaf_surname=Deretic, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817657.chap22-aff2]]}]]

/content/10.1128/9781555817657.chap22.tab22-1

Table 1

M. tuberculosis two-component signal transduction systems a

10.1128/9781555817657/tab22-1_thmb.gif

10.1128/9781555817657/tab22-1.gif

Table 1

M. tuberculosis two-component signal transduction systems a

/content/10.1128/9781555817657.chap22.tab22-2

Table 2

Summary of M. tuberculosisSTpK properties

10.1128/9781555817657/tab22-2_thmb.gif

10.1128/9781555817657/tab22-2.gif

Table 2

Summary of M. tuberculosisSTpK properties