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Volume 161, Issue 9

Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators Free

Abstract

Reversible phosphorylation of bacterial transcriptional regulators (TRs) belonging to the family of two-component systems (TCSs) is a well-established mechanism for regulating gene expression. Recent evidence points to the fact that reversible phosphorylation of bacterial TRs on other types of residue, i.e. serine, threonine, tyrosine and cysteine, is also quite common. The phosphorylation of the ester type (phospho-serine/threonine/tyrosine) is more stable than the aspartate phosphorylation of TCSs. The kinases which catalyse these phosphorylation events (Hanks-type serine/threonine protein kinases and bacterial protein tyrosine kinases) are also much more promiscuous than the TCS kinases, i.e. each of them can phosphorylate several substrate proteins. As a consequence, the dynamics and topology of the signal transduction networks depending on these kinases differ significantly from the TCSs. Here, we present an overview of different classes of bacterial TR phosphorylated and regulated by serine/threonine and tyrosine kinases. Particular attention is given to examples when serine/threonine and tyrosine kinases interact with TCSs, phosphorylating either the histidine kinases or the response regulators. We argue that these promiscuous kinases connect several signal transduction pathways and serve the role of signal integration.

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2015-09-01
2024-04-19
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References

  1. Aiba H., Mizuno T., Mizushima S. 1989; Transfer of phosphoryl group between two regulatory proteins involved in osmoregulatory expression of the ompF and ompC genes in Escherichia coli. J Biol Chem 264:8563–8567[PubMed]
     [Google Scholar]
  2. Alon U., Camarena L., Surette M. G., Aguera y Arcas B., Liu Y., Leibler S., Stock J. B. 1998; Response regulator output in bacterial chemotaxis. EMBO J 17:4238–4248 [View Article][PubMed]
     [Google Scholar]
  3. Alon U., Surette M. G., Barkai N., Leibler S. 1999; Robustness in bacterial chemotaxis. Nature 397:168–171 [View Article][PubMed]
     [Google Scholar]
  4. Baulard A. R., Betts J. C., Engohang-Ndong J., Quan S., McAdam R. A., Brennan P. J., Locht C., Besra G. S. 2000; Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem 275:28326–28331[PubMed]
     [Google Scholar]
  5. Belcheva A., Golemi-Kotra D. 2008; A close-up view of the VraSR two-component system. A mediator of Staphylococcus aureus response to cell wall damage. J Biol Chem 283:12354–12364 [View Article][PubMed]
     [Google Scholar]
  6. Bobay B. G., Benson L., Naylor S., Feeney B., Clark A. C., Goshe M. B., Strauch M. A., Thompson R., Cavanagh J. 2004; Evaluation of the DNA binding tendencies of the transition state regulator AbrB. Biochemistry 43:16106–16118 [View Article][PubMed]
     [Google Scholar]
  7. Canova M. J., Veyron-Churlet R., Zanella-Cleon I., Cohen-Gonsaud M., Cozzone A. J., Becchi M., Kremer L., Molle V. 2008; The Mycobacterium tuberculosis serine/threonine kinase PknL phosphorylates Rv2175c: mass spectrometric profiling of the activation loop phosphorylation sites and their role in the recruitment of Rv2175c. Proteomics 8:521–533 [View Article][PubMed]
     [Google Scholar]
  8. Canova M. J., Baronian G., Brelle S., Cohen-Gonsaud M., Bischoff M., Molle V. 2014; A novel mode of regulation of the Staphylococcus aureus vancomycin-resistance-associated response regulator VraR mediated by Stk1 protein phosphorylation. Biochem Biophys Res Commun 447:165–171 [View Article][PubMed]
     [Google Scholar]
  9. Chao J. D., Papavinasasundaram K. G., Zheng X., Chávez-Steenbock A., Wang X., Lee G. Q., Av-Gay Y. 2010; Convergence of Ser/Thr and two-component signaling to coordinate expression of the dormancy regulon in Mycobacterium tuberculosis. J Biol Chem 285:29239–29246 [View Article][PubMed]
     [Google Scholar]
  10. Cheung A. L., Nishina K. A., Trotonda M. P., Tamber S. 2008; The SarA protein family of Staphylococcus aureus. Int J Biochem Cell Biol 40:355–361 [View Article][PubMed]
     [Google Scholar]
  11. Chien Y., Manna A. C., Projan S. J., Cheung A. L. 1999; SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J Biol Chem 274:37169–37176 [View Article][PubMed]
     [Google Scholar]
  12. Chumsakul O., Takahashi H., Oshima T., Hishimoto T., Kanaya S., Ogasawara N., Ishikawa S. 2011; Genome-wide binding profiles of the Bacillus subtilis transition state regulator AbrB and its homolog Abh reveals their interactive role in transcriptional regulation. Nucleic Acids Res 39:414–428 [View Article][PubMed]
     [Google Scholar]
  13. Cohen-Gonsaud M., Barthe P., Canova M. J., Stagier-Simon C., Kremer L., Roumestand C., Molle V. 2009; The Mycobacterium tuberculosis Ser/Thr kinase substrate Rv2175c is a DNA-binding protein regulated by phosphorylation. J Biol Chem 284:19290–19300 [View Article][PubMed]
     [Google Scholar]
  14. Dardel F., Panvert M., Blanquet S., Fayat G. 1991; Locations of the metG and mrp genes on the physical map of Escherichia coli. J Bacteriol 173:3273[PubMed]
     [Google Scholar]
  15. DeBarber A. E., Mdluli K., Bosman M., Bekker L. G., Barry C. E. III 2000; Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 97:9677–9682 [View Article][PubMed]
     [Google Scholar]
  16. Derouiche A., Bidnenko V., Grenha R., Pigonneau N., Ventroux M., Franz-Wachtel M., Nessler S., Noirot-Gros M. F., Mijakovic I. 2013; Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain. Nucleic Acids Res 41:9371–9381 [View Article][PubMed]
     [Google Scholar]
  17. Derouiche A., Shi L., Bidnenko V., Ventroux M., Pigonneau N., Franz-Wachtel M., Kalantari A., Nessler S., Noirot-Gros M. F., Mijakovic I. 2015; Bacillus subtilis SalA is a phosphorylation-dependent transcription regulator that represses scoC and activates the production of the exoprotease AprE. Mol Microbiol [View Article][PubMed]
     [Google Scholar]
  18. Didier J. P., Cozzone A. J., Duclos B. 2010; Phosphorylation of the virulence regulator SarA modulates its ability to bind DNA in Staphylococcus aureus. FEMS Microbiol Lett 306:30–36 [View Article][PubMed]
     [Google Scholar]
  19. Federle M. J., McIver K. S., Scott J. R. 1999; A response regulator that represses transcription of several virulence operons in the group A streptococcus. J Bacteriol 181:3649–3657[PubMed]
     [Google Scholar]
  20. Forst S., Delgado J., Inouye M. 1989 Phosphorylation of OmpR by the osmosensor EnvZ modulates expression of the ompF and ompC genes in Escherichia coli. Proc Natl Acad Sci U S A 86:6052–6056 [View Article][PubMed]
     [Google Scholar]
  21. Fridman M., Williams G. D., Muzamal U., Hunter H., Siu K. W., Golemi-Kotra D. 2013; Two unique phosphorylation-driven signaling pathways crosstalk in Staphylococcus aureus to modulate the cell-wall charge: Stk1/Stp1 meets GraSR. Biochemistry 52:7975–7986 [View Article][PubMed]
     [Google Scholar]
  22. Fujita Y. 2009; Carbon catabolite control of the metabolic network in Bacillus subtilis. Biosci Biotechnol Biochem 73:245–259 [View Article][PubMed]
     [Google Scholar]
  23. Galperin M. Y. 2010; Diversity of structure and function of response regulator output domains. Curr Opin Microbiol 13:150–159 [View Article][PubMed]
     [Google Scholar]
  24. Gao R., Stock A. M. 2009; Biological insights from structures of two-component proteins. Annu Rev Microbiol 63:133–154 [View Article][PubMed]
     [Google Scholar]
  25. Gao R., Mack T. R., Stock A. M. 2007; Bacterial response regulators: versatile regulatory strategies from common domains. Trends Biochem Sci 32:225–234 [View Article][PubMed]
     [Google Scholar]
  26. Gustafsson M. C., Roitel O., Marshall K. R., Noble M. A., Chapman S. K., Pessegueiro A., Fulco A. J., Cheesman M. R., von Wachenfeldt C., Munro A. W. 2004; Expression, purification, and characterization of Bacillus subtilis cytochromes P450 CYP102A2 and CYP102A3: flavocytochrome homologues of P450 BM3 from Bacillus megaterium. Biochemistry 43:5474–5487 [View Article][PubMed]
     [Google Scholar]
  27. Hammerstrom T. G., Horton L. B., Swick M. C., Joachimiak A., Osipiuk J., Koehler T. M. 2015; Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity. Mol Microbiol 95:426–441 [View Article][PubMed]
     [Google Scholar]
  28. Hoch J. A., Varughese K. I. 2001; Keeping signals straight in phosphorelay signal transduction. J Bacteriol 183:4941–4949 [View Article][PubMed]
     [Google Scholar]
  29. Jers C., Kobir A., Søndergaard E. O., Jensen P. R., Mijakovic I. 2011; Bacillus subtilis two-component system sensory kinase DegS is regulated by serine phosphorylation in its input domain. PLoS One 6:e14653 [View Article][PubMed]
     [Google Scholar]
  30. Jiang S. M., Cieslewicz M. J., Kasper D. L., Wessels M. R. 2005; Regulation of virulence by a two-component system in group B streptococcus. J Bacteriol 187:1105–1113 [View Article][PubMed]
     [Google Scholar]
  31. Kobayashi K. 2007; Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis. Mol Microbiol 66:395–409 [View Article][PubMed]
     [Google Scholar]
  32. Kobir A., Poncet S., Bidnenko V., Delumeau O., Jers C., Zouhir S., Grenha R., Nessler S., Noirot P., Mijakovic I. 2014; Phosphorylation of Bacillus subtilis gene regulator AbrB modulates its DNA-binding properties. Mol Microbiol 92:1129–1141 [View Article][PubMed]
     [Google Scholar]
  33. Kumar A., Toledo J. C., Patel R. P., Lancaster J. R. Jr, Steyn A. J. 2007; Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci U S A 104:11568–11573 [View Article][PubMed]
     [Google Scholar]
  34. Laub M. T., Goulian M. 2007; Specificity in two-component signal transduction pathways. Annu Rev Genet 41:121–145 [View Article][PubMed]
     [Google Scholar]
  35. Lee T. R., Hsu H. P., Shaw G. C. 2001; Transcriptional regulation of the Bacillus subtilis bscR-CYP102A3 operon by the BscR repressor and differential induction of cytochrome CYP102A3 expression by oleic acid and palmitate. J Biochem 130:569–574 [View Article][PubMed]
     [Google Scholar]
  36. Leiba J., Hartmann T., Cluzel M. E., Cohen-Gonsaud M., Delolme F., Bischoff M., Molle V. 2012; A novel mode of regulation of the Staphylococcus aureus catabolite control protein A (CcpA) mediated by Stk1 protein phosphorylation. J Biol Chem 287:43607–43619 [View Article][PubMed]
     [Google Scholar]
  37. Leiba J., Carrère-Kremer S., Blondiaux N., Dimala M. M., Wohlkönig A., Baulard A., Kremer L., Molle V. 2014; The Mycobacterium tuberculosis transcriptional repressor EthR is negatively regulated by serine/threonine phosphorylation. Biochem Biophys Res Commun 446:1132–1138 [View Article][PubMed]
     [Google Scholar]
  38. Lentz O., Urlacher V., Schmid R. D. 2004; Substrate specificity of native and mutated cytochrome P450 (CYP102A3) from Bacillus subtilis. J Biotechnol 108:41–49 [View Article][PubMed]
     [Google Scholar]
  39. Lois A. F., Weinstein M., Ditta G. S., Helinski D. R. 1993; Autophosphorylation and phosphatase activities of the oxygen-sensing protein FixL of Rhizobium meliloti are coordinately regulated by oxygen. J Biol Chem 268:4370–4375[PubMed]
     [Google Scholar]
  40. Macek B., Mijakovic I., Olsen J. V., Gnad F., Kumar C., Jensen P. R., Mann M. 2007; The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis. Mol Cell Proteomics 6:697–707 [View Article][PubMed]
     [Google Scholar]
  41. Mäder U., Antelmann H., Buder T., Dahl M. K., Hecker M., Homuth G. 2002; Bacillus subtilis functional genomics: genome-wide analysis of the DegS-DegU regulon by transcriptomics and proteomics. Mol Genet Genomics 268:455–467 [View Article][PubMed]
     [Google Scholar]
  42. Mijakovic I., Deutscher J. 2015; Protein-tyrosine phosphorylation in Bacillus subtilis: a 10-year retrospective. Front Microbiol 6:18 [View Article][PubMed]
     [Google Scholar]
  43. Mijakovic I., Poncet S., Galinier A., Monedero V., Fieulaine S., Janin J., Nessler S., Marquez J. A., Scheffzek K., other authors. 2002; Pyrophosphate-producing protein dephosphorylation by HPr kinase/phosphorylase: a relic of early life?. Proc Natl Acad Sci U S A 99:13442–13447 [View Article][PubMed]
     [Google Scholar]
  44. Molle V., Kremer L. 2010; Division and cell envelope regulation by Ser/Thr phosphorylation: Mycobacterium shows the way. Mol Microbiol 75:1064–1077 [View Article][PubMed]
     [Google Scholar]
  45. Msadek T., Kunst F., Henner D., Klier A., Rapoport G., Dedonder R. 1990; Signal transduction pathway controlling synthesis of a class of degradative enzymes in Bacillus subtilis: expression of the regulatory genes and analysis of mutations in degS and degU. J Bacteriol 172:824–834[PubMed]
     [Google Scholar]
  46. Ninfa A. J., Magasanik B. 1986; Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli. Proc Natl Acad Sci U S A 83:5909–5913 [View Article][PubMed]
     [Google Scholar]
  47. Nixon B. T., Ronson C. W., Ausubel F. M. 1986; Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genes ntrB and ntrC. Proc Natl Acad Sci U S A 83:7850–7854 [View Article][PubMed]
     [Google Scholar]
  48. Ogura M., Yamaguchi H., Yoshida Ki Fujita,Y., Tanaka T. 2001; DNA microarray analysis of Bacillus subtilis DegU, ComA and PhoP regulons: an approach to comprehensive analysis of B.subtilis two-component regulatory systems. Nucleic Acids Res 29:3804–3813 [View Article][PubMed]
     [Google Scholar]
  49. Ogura M., Matsuzawa A., Yoshikawa H., Tanaka T. 2004; Bacillus subtilis SalA (YbaL) negatively regulates expression of scoC, which encodes the repressor for the alkaline exoprotease gene, aprE. J Bacteriol 186:3056–3064 [View Article][PubMed]
     [Google Scholar]
  50. Ohlsen K., Donat S. 2010; The impact of serine/threonine phosphorylation in Staphylococcus aureus. Int J Med Microbiol 300:137–141 [View Article][PubMed]
     [Google Scholar]
  51. Ong C. L., Potter A. J., Trappetti C., Walker M. J., Jennings M. P., Paton J. C., McEwan A. G. 2013; Interplay between manganese and iron in pneumococcal pathogenesis: role of the orphan response regulator RitR. Infect Immun 81:421–429 [View Article][PubMed]
     [Google Scholar]
  52. Park H. D., Guinn K. M., Harrell M. I., Liao R., Voskuil M. I., Tompa M., Schoolnik G. K., Sherman D. R. 2003; Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol Microbiol 48:833–843 [View Article][PubMed]
     [Google Scholar]
  53. Prisic S., Dankwa S., Schwartz D., Chou M. F., Locasale J. W., Kang C. M., Bemis G., Church G. M., Steen H., Husson R. N. 2010; Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases. Proc Natl Acad Sci U S A 107:7521–7526 [View Article][PubMed]
     [Google Scholar]
  54. Rajagopal L., Vo A., Silvestroni A., Rubens C. E. 2006; Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae. Mol Microbiol 62:941–957 [View Article][PubMed]
     [Google Scholar]
  55. Rampersaud A., Harlocker S. L., Inouye M. 1994; The OmpR protein of Escherichia coli binds to sites in the ompF promoter region in a hierarchical manner determined by its degree of phosphorylation. J Biol Chem 269:12559–12566[PubMed]
     [Google Scholar]
  56. Roberts D. M., Liao R. P., Wisedchaisri G., Hol W. G., Sherman D. R. 2004; Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis. J Biol Chem 279:23082–23087 [View Article][PubMed]
     [Google Scholar]
  57. Schmidt A., Trentini D. B., Spiess S., Fuhrmann J., Ammerer G., Mechtler K., Clausen T. 2014; Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response. Mol Cell Proteomics 13:537–550 [View Article][PubMed]
     [Google Scholar]
  58. Seidl K., Stucki M., Ruegg M., Goerke C., Wolz C., Harris L., Berger-Bächi B., Bischoff M. 2006; Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance. Antimicrob Agents Chemother 50:1183–1194 [View Article][PubMed]
     [Google Scholar]
  59. Shi L., Pigeonneau N., Ravikumar V., Dobrinic P., Macek B., Franjevic D., Noirot-Gros M. F., Mijakovic I. 2014a; Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues. Front Microbiol 5:495 [View Article][PubMed]
     [Google Scholar]
  60. Shi L., Ji B., Kolar-Znika L., Boskovic A., Jadeau F., Combet C., Grangeasse C., Franjevic D., Talla E., Mijakovic I. 2014b; Evolution of bacterial protein-tyrosine kinases and their relaxed specificity toward substrates. Genome Biol Evol 6:800–817 [View Article][PubMed]
     [Google Scholar]
  61. Skerker J. M., Perchuk B. S., Siryaporn A., Lubin E. A., Ashenberg O., Goulian M., Laub M. T. 2008; Rewiring the specificity of two-component signal transduction systems. Cell 133:1043–1054 [View Article][PubMed]
     [Google Scholar]
  62. Soufi B., Kumar C., Gnad F., Mann M., Mijakovic I., Macek B. 2010; Stable isotope labeling by amino acids in cell culture (SILAC) applied to quantitative proteomics of Bacillus subtilis. J Proteome Res 9:3638–3646 [View Article][PubMed]
     [Google Scholar]
  63. Stock A. M., Robinson V. L., Goudreau P. N. 2000; Two-component signal transduction. Annu Rev Biochem 69:183–215 [View Article][PubMed]
     [Google Scholar]
  64. Sun F., Ding Y., Ji Q., Liang Z., Deng X., Wong C. C., Yi C., Zhang L., Xie S., other authors. 2012; Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance. Proc Natl Acad Sci U S A 109:15461–15466 [View Article][PubMed]
     [Google Scholar]
  65. Szurmant H., Hoch J. A. 2010; Interaction fidelity in two-component signaling. Curr Opin Microbiol 13:190–197 [View Article][PubMed]
     [Google Scholar]
  66. Szurmant H., White R. A., Hoch J. A. 2007; Sensor complexes regulating two-component signal transduction. Curr Opin Struct Biol 17:706–715 [View Article][PubMed]
     [Google Scholar]
  67. Tamber S., Schwartzman J., Cheung A. L. 2010; Role of PknB kinase in antibiotic resistance and virulence in community-acquired methicillin-resistant. Staphylococcus aureus strain USA300. Infect Immun 78:3637–3646 [View Article][PubMed]
     [Google Scholar]
  68. Throup J. P., Koretke K. K., Bryant A. P., Ingraham K. A., Chalker A. F., Ge Y., Marra A., Wallis N. G., Brown J. R., other authors. 2000; A genomic analysis of two-component signal transduction in Streptococcus pneumoniae. Mol Microbiol 35:566–576 [View Article][PubMed]
     [Google Scholar]
  69. Truong-Bolduc Q. C., Hooper D. C. 2010; Phosphorylation of MgrA and its effect on expression of the NorA and NorB efflux pumps of Staphylococcus aureus. J Bacteriol 192:2525–2534 [View Article][PubMed]
     [Google Scholar]
  70. Truong-Bolduc Q. C., Ding Y., Hooper D. C. 2008; Posttranslational modification influences the effects of MgrA on norA expression in Staphylococcus aureus. J Bacteriol 190:7375–7381 [View Article][PubMed]
     [Google Scholar]
  71. Ulijasz A. T., Andes D. R., Glasner J. D., Weisblum B. 2004; Regulation of iron transport in Streptococcus pneumoniae by RitR, an orphan response regulator. J Bacteriol 186:8123–8136 [View Article][PubMed]
     [Google Scholar]
  72. Ulijasz A. T., Falk S. P., Weisblum B. 2009; Phosphorylation of the RitR DNA-binding domain by a Ser-Thr phosphokinase: implications for global gene regulation in the streptococci. Mol Microbiol 71:382–390 [View Article][PubMed]
     [Google Scholar]
  73. Valle J., Toledo-Arana A., Berasain C., Ghigo J. M., Amorena B., Penadés J. R., Lasa I. 2003; SarA and not sigmaB is essential for biofilm development by Staphylococcus aureus. Mol Microbiol 48:1075–1087 [View Article][PubMed]
     [Google Scholar]
  74. Verhamme D. T., Kiley T. B., Stanley-Wall N. R. 2007; DegU co-ordinates multicellular behaviour exhibited by Bacillus subtilis. Mol Microbiol 65:554–568 [View Article][PubMed]
     [Google Scholar]
  75. Vitale G., Fabre E., Hurt E. C. 1996; NBP35 encodes an essential and evolutionary conserved protein in Saccharomyces cerevisiae with homology to a superfamily of bacterial ATPases. Gene 178:97–106 [View Article][PubMed]
     [Google Scholar]
  76. Whidbey C., Harrell M. I., Burnside K., Ngo L., Becraft A. K., Iyer L. M., Aravind L., Hitti J., Adams Waldorf K. M., Rajagopal L. 2013; A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta. J Exp Med 210:1265–1281 [View Article][PubMed]
     [Google Scholar]
  77. Wright D. P., Ulijasz A. T. 2014; Regulation of transcription by eukaryotic-like serine-threonine kinases and phosphatases in Gram-positive bacterial pathogens. Virulence 5:863–885 [View Article][PubMed]
     [Google Scholar]
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Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators
Microbiology 161, 1720 (2015); https://doi.org/10.1099/mic.0.000148
/content/journal/micro/10.1099/mic.0.000148
/content/journal/micro/10.1099/mic.0.000148
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