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Abstract
Tyrosine kinases and phosphatases are enzymes that regulate many bacterial proteins involved in promoting infection. Tyrosine kinases work by tacking phosphate molecules onto specific amino acids, while phosphatases take them off. Sarah Whitmore and Richard Lamont of the University of Louisville in Kentucky, USA, have now reviewed the structure and function of these enzymes, which contribute to bacterial virulence, including that of Porphyromonas gingivalis and Streptococcus gordonii. They explain that tyrosine kinases help regulate the production of specialized sugars that bacteria use to interact with target cells; many bacterial phosphatases, however, actively sabotage host cell signaling processes. The authors conclude that future work will provide a better understanding of these important enzymes and should help guide development of more effective antibacterial drugs.
Keywords
oral biofilm
/
Porphyromonas gingivalis
/
Streptococcus
/
tyrosine phosphorylation
/
virulence
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Sarah E Whitmore, Richard J Lamont.
Tyrosine phosphorylation and bacterial virulence.
International Journal of Oral Science, 2012, 4(1): 1-6 DOI:10.1038/ijos.2012.6
| [1] |
Backert S, Selbach M. Tyrosine-phosphorylated bacterial effector proteins: the enemies within. Trends Microbiol, 2005, 13(10): 476-484.
|
| [2] |
Aivaliotis M, Macek B, Gnad F. Ser/Thr/Tyr protein phosphorylation in the archaeon Halobacterium salinarum–a representative of the third domain of life. PLoS One, 2009, 4(3): e4777.
|
| [3] |
Cozzone AJ, Grangeasse C, Doublet P. Protein phosphorylation on tyrosine in bacteria. Arch Microbiol, 2004, 181(3): 171-181.
|
| [4] |
Cozzone AJ. Role of protein phosphorylation on serine/threonine and tyrosine in the virulence of bacterial pathogens. J Mol Microbiol Biotechnol, 2005, 9(3/4): 198-213.
|
| [5] |
Wiley DJ, Nordfeldth R, Rosenzweig J. The Ser/Thr kinase activity of the Yersinia protein kinase A (YpkA) is necessary for full virulence in the mouse, mollifying phagocytes, and disrupting the eukaryotic cytoskeleton. Microb Pathog, 2006, 40(5): 234-243.
|
| [6] |
Gao X, Wan F, Mateo K. Bacterial effector binding to ribosomal protein s3 subverts NF-κB function. PLoS Pathog, 2009, 5(12): e1000708.
|
| [7] |
Royan SV, Jones RM, Koutsouris A. Enteropathogenic E. coli non-LEE encoded effectors NleH1 and NleH2 attenuate NF-κB activation. Mol Microbiol, 2010, 78(5): 1232-1245.
|
| [8] |
Bainbridge B, Verma RK, Eastman C. Role of Porphyromonas gingivalis phosphoserine phosphatase enzyme SerB in inflammation, immune response, and induction of alveolar bone resorption in rats. Infect Immun, 2010, 78(11): 4560-4569.
|
| [9] |
Hasegawa Y, Tribble GD, Baker HV. Role of Porphyromonas gingivalis SerB in gingival epithelial cell cytoskeletal remodeling and cytokine production. Infect Immun, 2008, 76(6): 2420-2427.
|
| [10] |
Tribble GD, Mao S, James CE. A Porphyromonas gingivalis haloacid dehalogenase family phosphatase interacts with human phosphoproteins and is important for invasion. Proc Natl Acad Sci USA, 2006, 103(29): 11027-11032.
|
| [11] |
Manai M, Cozzone AJ. Endogenous protein phosphorylation in Escherichia coli extracts. Biochem Biophys Res Commun, 1982, 107(3): 981-988.
|
| [12] |
Zhang ZY. Functional studies of protein tyrosine phosphatases with chemical approaches. Biochim Biophys Acta, 2005, 1754(1/2): 100-107.
|
| [13] |
Stulke J. More than just activity control: phosphorylation may control all aspects of a protein's properties. Mol Microbiol, 2010, 77(2): 273-275.
|
| [14] |
Ge R, Sun X, Xiao C. Phosphoproteome analysis of the pathogenic bacterium Helicobacter pylori reveals over-representation of tyrosine phosphorylation and multiply phosphorylated proteins. Proteomics, 2011, 11(8): 1449-1461.
|
| [15] |
Parker JL, Jones AM, Serazetdinova L. Analysis of the phosphoproteome of the multicellular bacterium Streptomyces coelicolor A3(2) by protein/peptide fractionation, phosphopeptide enrichment and high-accuracy mass spectrometry. Proteomics, 2010, 10(13): 2486-2497.
|
| [16] |
Schmidl SR, Gronau K, Pietack N. The phosphoproteome of the minimal bacterium Mycoplasma pneumoniae: analysis of the complete known Ser/Thr kinome suggests the existence of novel kinases. Mol Cell Proteomics, 2010, 9(6): 1228-1242.
|
| [17] |
Sun X, Ge F, Xiao CL. Phosphoproteomic analysis reveals the multiple roles of phosphorylation in pathogenic bacterium Streptococcus pneumoniae. . J Proteome Res, 2010, 9(1): 275-282.
|
| [18] |
Lin MH, Hsu TL, Lin SY. Phosphoproteomics of Klebsiella pneumoniae NTUH-K2044 reveals a tight link between tyrosine phosphorylation and virulence. Mol Cell Proteomics, 2009, 8(12): 2613-2623.
|
| [19] |
Ravichandran A, Sugiyama N, Tomita M. Ser/Thr/Tyr phosphoproteome analysis of pathogenic and non-pathogenic Pseudomonas species. Proteomics, 2009, 9(10): 2764-2775.
|
| [20] |
Voisin S, Watson DC, Tessier L. The cytoplasmic phosphoproteome of the gram-negative bacterium Campylobacter jejuni: evidence for modification by unidentified protein kinases. Proteomics, 2007, 7(23): 4338-4348.
|
| [21] |
Soufi B, Gnad F, Jensen PR. The Ser/Thr/Tyr phosphoproteome of Lactococcus lactis IL1403 reveals multiply phosphorylated proteins. Proteomics, 2008, 8(17): 3486-3493.
|
| [22] |
Macek B, Mijakovic I, Olsen JV. The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis. . Mol Cell Proteomics, 2007, 6(4): 697-707.
|
| [23] |
Macek B, Gnad F, Soufi B. Phosphoproteome analysis of E. coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation. Mol Cell Proteomics, 2008, 7(2): 299-307.
|
| [24] |
Soufi B, Jers C, Hansen ME. Insights from site-specific phosphoproteomics in bacteria. Biochim Biophys Acta, 2008, 1784(1): 186-192.
|
| [25] |
Grangeasse C, Cozzone AJ, Deutscher J. Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology. Trends Biochem Sci, 2007, 32(2): 86-94.
|
| [26] |
Jers C, Pedersen MM, Paspaliari DK. Bacillus subtilis BY-kinase PtkA controls enzyme activity and localization of its protein substrates. Mol Microbiol, 2010, 77(2): 287-299.
|
| [27] |
Tiganis T. Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor. IUBMB Life, 2002, 53(1): 3-14.
|
| [28] |
Bliska JB. Yop effectors of Yersinia spp. and actin rearrangements. Trends Microbiol, 2000, 8(5): 205-208.
|
| [29] |
Black DS, Montagna LG, Zitsmann S. Identification of an amino-terminal substrate-binding domain in the Yersinia tyrosine phosphatase that is required for efficient recognition of focal adhesion targets. Mol Microbiol, 1998, 29(5): 1263-1274.
|
| [30] |
Persson C, Nordfelth R, Andersson K. Localization of the Yersinia PTPase to focal complexes is an important virulence mechanism. Mol Microbiol, 1999, 33(4): 828-838.
|
| [31] |
Persson C, Carballeira N, Wolf-Watz H. The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. EMBO J, 1997, 16(9): 2307-2318.
|
| [32] |
Lin SL, Le TX, Cowen DS. SptP, a Salmonella typhimurium type III-secreted protein, inhibits the mitogen-activated protein kinase pathway by inhibiting Raf activation. Cell Microbiol, 2003, 5(4): 267-275.
|
| [33] |
Kaniga K, Uralil J, Bliska JB. A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium. . Mol Microbiol, 1996, 21(3): 633-641.
|
| [34] |
Arbibe L, Kim DW, Batsche E. An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses. Nat Immunol, 2007, 8(1): 47-56.
|
| [35] |
Koul A, Choidas A, Treder M. Cloning and characterization of secretory tyrosine phosphatases of Mycobacterium tuberculosis. . J Bacteriol, 2000, 182(19): 5425-5432.
|
| [36] |
Bach H, Papavinasasundaram KG, Wong D. Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe, 2008, 3(5): 316-322.
|
| [37] |
Singh B, Singh G, Trajkovic V. Intracellular expression of Mycobacterium tuberculosis-specific 10-kDa antigen down-regulates macrophage B7.1 expression and nitric oxide release. Clin Exp Immunol, 2003, 134(1): 70-77.
|
| [38] |
Castandet J, Prost JF, Peyron P. Tyrosine phosphatase MptpA of Mycobacterium tuberculosis inhibits phagocytosis and increases actin polymerization in macrophages. Res Microbiol, 2005, 156(10): 1005-1013.
|
| [39] |
Kastner R, Dussurget O, Archambaud C. LipA, a tyrosine and lipid phosphatase involved in the virulence of Listeria monocytogenes. . Infect Immun, 2011, 79(6): 2489-2498.
|
| [40] |
Vincent C, Doublet P, Grangeasse C. Cells of Escherichia coli contain a protein-tyrosine kinase, Wzc, and a phosphotyrosine-protein phosphatase, Wzb. J Bacteriol, 1999, 181(11): 3472-3477.
|
| [41] |
Morona JK, Paton JC, Miller DC. Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in Streptococcus pneumoniae. . Mol Microbiol, 2000, 35(6): 1431-1442.
|
| [42] |
Bender MH, Yother J. CpsB is a modulator of capsule-associated tyrosine kinase activity in Streptococcus pneumoniae. . J Biol Chem, 2001, 276(51): 47966-47974.
|
| [43] |
Weiser JN, Bae D, Epino H. Changes in availability of oxygen accentuate differences in capsular polysaccharide expression by phenotypic variants and clinical isolates of Streptococcus pneumoniae. . Infect Immun, 2001, 69(9): 5430-5439.
|
| [44] |
Wugeditsch T, Paiment A, Hocking J. Phosphorylation of Wzc, a tyrosine autokinase, is essential for assembly of group 1 capsular polysaccharides in Escherichia coli. . J Biol Chem, 2001, 276(4): 2361-2371.
|
| [45] |
Niemeyer D, Becker A. The molecular weight distribution of succinoglycan produced by Sinorhizobium meliloti is influenced by specific tyrosine phosphorylation and ATPase activity of the cytoplasmic domain of the ExoP protein. J Bacteriol, 2001, 183(17): 5163-5170.
|
| [46] |
Nakar D, Gutnick DL. Involvement of a protein tyrosine kinase in production of the polymeric bioemulsifier emulsan from the oil-degrading strain Acinetobacter lwoffii RAG-1. J Bacteriol, 2003, 185(3): 1001-1009.
|
| [47] |
Ueda A, Wood TK. Connecting quorum sensing, c-di-GMP, pel polysaccharide, and biofilm formation in Pseudomonas aeruginosa through tyrosine phosphatase TpbA (PA3885). PLoS Pathog, 2009, 5(6): e1000483.
|
| [48] |
Ueda A, Wood TK. Tyrosine phosphatase TpbA of Pseudomonas aeruginosa controls extracellular DNA via cyclic diguanylic acid concentrations. Environ Microbiol, 2010, 2(3): 449-455.
|
| [49] |
Maeda K, Tribble GD, Tucker CM. A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes. Mol Microbiol, 2008, 69(5): 1153-1164.
|
| [50] |
Simionato MR, Tucker CM, Kuboniwa M. Porphyromonas gingivalis genes involved in community development with Streptococcus gordonii. . Infect Immun, 2006, 74(11): 6419-6428.
|
| [51] |
Chawla A, Hirano T, Bainbridge BW. Community signalling between Streptococcus gordonii and Porphyromonas gingivalis is controlled by the transcriptional regulator CdhR. Mol Microbiol, 2010, 78(6): 1510-1522.
|
| [52] |
Olivares-Illana V, Meyer P, Bechet E. Structural basis for the regulation mechanism of the tyrosine kinase CapB from Staphylococcus aureus. . PLoS Biol, 2008, 6(6): e143.
|
| [53] |
Lee DC, Zheng J, She YM. Structure of Escherichia coli tyrosine kinase Etk reveals a novel activation mechanism. EMBO J, 2008, 27(12): 1758-1766.
|
| [54] |
Cozzone AJ. Bacterial tyrosine kinases: novel targets for antibacterial therapy?. Trends Microbiol, 2009, 17(2): 536-543.
|
| [55] |
Hill J, Samuel JE. Coxiella burnetii acid phosphatase inhibits the release of reactive oxygen intermediates in polymorphonuclear leukocytes. Infect Immun, 2011, 79(1): 414-420.
|
| [56] |
Li YP, Curley G, Lopez M. Protein-tyrosine phosphatase activity of Coxiella burnetii that inhibits human neutrophils. Acta Virol, 1996, 40(5/6): 263-272.
|
| [57] |
Cowley SC, Babakaiff R, Av-Gay Y. Expression and localization of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Res Microbiol, 2002, 153(4): 233-241.
|
| [58] |
Walburger A, Koul A, Ferrari G. Protein kinase G from pathogenic Mycobacteria promotes survival within macrophages. Science, 2004, 304(5678): 1800-1804.
|
| [59] |
Arricau N, Hermant D, Waxin H. Molecular characterization of the Salmonella typhi StpA protein that is related to both Yersinia YopE cytotoxin and YopH tyrosine phosphatase. Res Microbiol, 1997, 148(1): 21-26.
|
| [60] |
Murli S, Watson RO, Galan JE. Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells. Cell Microbiol, 2001, 3(12): 795-810.
|
| [61] |
Reiterer V, Grossniklaus L, Tschon T. Shigella flexneri type III secreted effector OspF reveals new crosstalks of proinflammatory signaling pathways during bacterial infection. Cell Signal, 2011, 23(7): 1188-1196.
|
| [62] |
Groves E, Rittinger K, Amstutz M. Sequestering of Rac by the Yersinia effector YopO blocks Fcγ receptor-mediated phagocytosis. J Biol Chem, 2010, 285(6): 4087-4098.
|
| [63] |
Grangeasse C, Doublet P, Vincent C. Functional characterization of the low-molecular-mass phosphotyrosine-protein phosphatase of Acinetobacter johnsonii. . J Mol Biol, 1998, 278(2): 339-347.
|
| [64] |
Mijakovic I, Petranovic D, Bottini N. Protein-tyrosine phosphorylation in Bacillus subtilis. . J Mol Microbiol Biotechnol, 2005, 9(3/4): 189-197.
|
| [65] |
Mijakovic I, Petranovic D, Macek B. Bacterial single-stranded DNA-binding proteins are phosphorylated on tyrosine. Nucleic Acids Res, 2006, 34(5): 1588-1596.
|
| [66] |
Wu J, Ohta N, Zhao JL. A novel bacterial tyrosine kinase essential for cell division and differentiation. Proc Natl Acad Sci USA, 1999, 96(23): 13068-13073.
|
| [67] |
Bugert P, Geider K. Characterization of the amsI gene product as a low molecular weight acid phosphatase controlling exopolysaccharide synthesis of Erwinia amylovora. . FEBS Lett, 1997, 400(2): 252-256.
|
| [68] |
Reid AN, Whitfield C. Functional analysis of conserved gene products involved in assembly of Escherichia coli capsules and exopolysaccharides: evidence for molecular recognition between Wza and Wzc for colanic acid biosynthesis. J Bacteriol, 2005, 187(15): 5470-5481.
|
| [69] |
Ilan O, Bloch Y, Frankel G. Protein tyrosine kinases in bacterial pathogens are associated with virulence and production of exopolysaccharide. EMBO J, 1999, 18(12): 3241-3248.
|
| [70] |
Preneta R, Jarraud S, Vincent C. Isolation and characterization of a protein-tyrosine kinase and a phosphotyrosine-protein phosphatase from Klebsiella pneumoniae. . Comp Biochem Physiol B Biochem Mol Biol, 2002, 131(1): 103-112.
|
| [71] |
Thomasson B, Link J, Stassinopoulos AG. MglA, a small GTPase, interacts with a tyrosine kinase to control type IV pili-mediated motility and development of Myxococcus xanthus. . Mol Microbiol, 2002, 46(5): 1399-1413.
|
| [72] |
Zhao X, Lam JS. WaaP of Pseudomonas aeruginosa is a novel eukaryotic type protein-tyrosine kinase as well as a sugar kinase essential for the biosynthesis of core lipopolysaccharide. J Biol Chem, 2002, 277(7): 4722-4730.
|
| [73] |
South SL, Nichols R, Montie TC. Tyrosine kinase activity in Pseudomonas aeruginosa. . Mol Microbiol, 1994, 12(6): 903-910.
|
| [74] |
Huang J, Carney BF, Denny TP. A complex network regulates expression of eps and other virulence genes of Pseudomonas solanacearum. . J Bacteriol, 1995, 177(5): 1259-1267.
|
| [75] |
Huang J, Schell M. Molecular characterization of the eps gene cluster of Pseudomonas solanacearum and its transcriptional regulation at a single promoter. Mol Microbiol, 1995, 16(5): 977-989.
|
| [76] |
Ostrovsky PC, Maloy S. Protein phosphorylation on serine, threonine, and tyrosine residues modulates membrane-protein interactions and transcriptional regulation in Salmonella typhimurium. . Genes Dev, 1995, 9(16): 2034-2041.
|
| [77] |
Jofre E, Becker A. Production of succinoglycan polymer in Sinorhizobium meliloti is affected by SMb21506 and requires the N-terminal domain of ExoP. Mol Plant Microbe Interact, 2009, 22(12): 1656-1668.
|
| [78] |
Gruszczyk J, Fleurie A, Olivares-Illana V. Structure analysis of the Staphylococcus aureus UDP-N-acetyl-mannosamine dehydrogenase Cap5O Involved in capsular polysaccharide biosynthesis. J Biol Chem, 2011, 286(19): 17112-17121.
|
| [79] |
Rubens CE, Heggen LM, Haft RF. Identification of cpsD, a gene essential for type III capsule expression in group B streptococci. Mol Microbiol, 1993, 8(5): 843-855.
|
| [80] |
Morona JK, Morona R, Miller DC. Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae. . J Bacteriol, 2003, 185(10): 3009-3019.
|
| [81] |
Minic Z, Marie C, Delorme C. Control of EpsE, the phosphoglycosyltransferase initiating exopolysaccharide synthesis in Streptococcus thermophilus, by EpsD tyrosine kinase. J Bacteriol, 2007, 189(4): 1351-1357.
|
| [82] |
Matsumoto A, Hong SK, Ishizuka H. Phosphorylation of the AfsR protein involved in secondary metabolism in Streptomyces species by a eukaryotic-type protein kinase. Gene, 1994, 146(1): 47-56.
|
| [83] |
Lee Y, Kim K, Suh JW. Binding study of AfsK, a Ser/Thr kinase from Streptomyces coelicolor A3(2) and S-adenosyl-L-methionine. FEMS Microbiol Lett, 2007, 266(2): 236-240.
|
| [84] |
Kumagai T, Kihara H, Watanabe W. A novel tyrosine-phosphorylated protein inhibiting the growth of Streptomyces cells. Biochem Biophys Res Commun, 2009, 385(4): 534-538.
|