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

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

Preview this chapter:
Zoom in

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

| /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap22-2.gif


This chapter covers two types of regulatory signal transduction elements in : (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 to kill the murine host or enhances the growth of the mutant strains in mice or macrophages may reflect evolutionary adaptations of 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. 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 . 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
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


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: 1191911924..
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.


Generic image for table
Table 1

two-component signal transduction systems

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
Generic image for table
Table 2

Summary of STpK properties

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

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error