1887

Abstract

MtrAB is a highly conserved two-component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular and links antibiotic production to sporulation in the filamentous Chloramphenicol biosynthesis is directly regulated by MtrA in and deletion of constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in , MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster-situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of switches on the production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and can be used to upregulate antibiotic production in distantly related streptomycetes.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000524
2017-10-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/163/10/1415.html?itemId=/content/journal/micro/10.1099/mic.0.000524&mimeType=html&fmt=ahah

References

  1. van der Meij A, Worsley SF, Hutchings MI, van Wezel GP. Chemical ecology of antibiotic production by actinomycetes. FEMS Microbiol Rev 2017; 41:392–416 [View Article][PubMed]
    [Google Scholar]
  2. Devine R, Hutchings MI, Holmes NA. Future directions for the discovery of antibiotics from actinomycete bacteria. Emerg Top Life Sci 2017; 1:1–12 [View Article]
    [Google Scholar]
  3. Som NF, Heine D, Holmes NA, Munnoch JT, Chandra G et al. The conserved actinobacterial two-component system MtrAB coordinates chloramphenicol production with sporulation in Streptomyces venezuelae NRRL B-65442. Front Microbiol 2017; 8:1237–11 [View Article][PubMed]
    [Google Scholar]
  4. Hoskisson PA, Hutchings MI. MtrAB–LpqB: a conserved three-component system in actinobacteria?. Trends Microbiol 2006; 14:444–449 [View Article]
    [Google Scholar]
  5. Purushotham G, Sarva KB, Blaszczyk E, Rajagopalan M, Madiraju MV. Mycobacterium tuberculosis oriC sequestration by MtrA response regulator. Mol Microbiol 2015; 98:586–604 [View Article][PubMed]
    [Google Scholar]
  6. Labeda DP, Goodfellow M, Brown R, Ward AC, Lanoot B et al. Phylogenetic study of the species within the family Streptomycetaceae. Antonie van Leeuwenhoek 2012; 101:73–104 [View Article][PubMed]
    [Google Scholar]
  7. Clark LC, Seipke RF, Prieto P, Willemse J, van Wezel GP et al. Mammalian cell entry genes in Streptomyces may provide clues to the evolution of bacterial virulence. Sci Rep 2013; 3:1109 [View Article][PubMed]
    [Google Scholar]
  8. Gust B, Challis GL, Fowler K, Kieser T, Chater KF. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc Natl Acad Sci USA 2003; 100:1541–1546 [View Article][PubMed]
    [Google Scholar]
  9. Nguyen HT, Wolff KA, Cartabuke RH, Ogwang S, Nguyen L. A lipoprotein modulates activity of the MtrAB two-component system to provide intrinsic multidrug resistance, cytokinetic control and cell wall homeostasis in Mycobacterium. Mol Microbiol 2010; 76:348–364 [View Article][PubMed]
    [Google Scholar]
  10. Gregory MA, Till R, Smith MC. Integration site for Streptomyces phage φBT1 and development of site-specific integrating vectors. J Bacteriol 2003; 185:5320–5323 [View Article][PubMed]
    [Google Scholar]
  11. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA. Practical Streptomyces Genetics John Innes Foundation; Norwich: 2000
    [Google Scholar]
  12. Munnoch JT, Martinez MTP, Svistunenko DA, Crack JC, Le Brun NE et al. Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily. Sci Rep 2016; 6:29495
    [Google Scholar]
  13. Nicol JW, Helt GA, Blanchard SG, Raja A, Loraine AE. The Integrated Genome Browser: free software for distribution and exploration of genome-scale datasets. Bioinformatics 2009; 25:2730–2731 [View Article][PubMed]
    [Google Scholar]
  14. Tschowri N, Schumacher MA, Schlimpert S, Chinnam NB, Findlay KC et al. Tetrameric c-di-GMP mediates effective transcription factor dimerization to control Streptomyces development. Cell 2014; 158:1136–1147 [View Article][PubMed]
    [Google Scholar]
  15. Molle V, Palframan WJ, Findlay KC, Buttner MJ. WhiD and WhiB, homologous proteins required for different stages of sporulation in Streptomyces coelicolor A3(2). J Bacteriol 2000; 182:1286–1295 [View Article][PubMed]
    [Google Scholar]
  16. Bush MJ, Bibb MJ, Chandra G, Findlay KC, Buttner MJ. Genes required for aerial growth, cell division, and chromosome segregation are targets of WhiA before sporulation in Streptomyces venezuelae. MBio 2013; 4:e00684-13 [View Article][PubMed]
    [Google Scholar]
  17. Fowler-Goldsworthy K, Gust B, Mouz S, Chandra G, Findlay KC et al. The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2). Microbiology 2011; 157:1312–1328 [View Article][PubMed]
    [Google Scholar]
  18. Challis GL. Exploitation of the Streptomyces coelicolor A3(2) genome sequence for discovery of new natural products and biosynthetic pathways. J Ind Microbiol Biotechnol 2014; 41:219–232 [View Article][PubMed]
    [Google Scholar]
  19. Van Keulen G, Dyson PJ. Production of specialized metabolites by Streptomyces coelicolor A3(2). Adv Applied Microbiol 2014; 89:217–266
    [Google Scholar]
  20. Withall DM, Haynes SW, Challis GL. Stereochemistry and mechanism of undecylprodigiosin oxidative carbocyclization to streptorubin B by the rieske oxygenase RedG. J Am Chem Soc 2015; 137:7889–7897 [View Article][PubMed]
    [Google Scholar]
  21. Tran NT, Den Hengst CD, Gomez-Escribano JP, Buttner MJ. Identification and characterization of CdgB, a diguanylate cyclase involved in developmental processes in Streptomyces coelicolor. J Bacteriol 2011; 193:3100–3108 [View Article][PubMed]
    [Google Scholar]
  22. Molle V, Buttner MJ. Different alleles of the response regulator gene bldM arrest Streptomyces coelicolor development at distinct stages. Mol Microbiol 2000; 36:1265–1278 [View Article]
    [Google Scholar]
  23. Al-Bassam MM, Bibb MJ, Bush MJ, Chandra G, Buttner MJ. Response regulator heterodimer formation controls a key stage in Streptomyces development. PLoS Genet 2014; 10:e1004554 [View Article][PubMed]
    [Google Scholar]
  24. Elliot MA, Karoonuthaisiri N, Huang J, Bibb MJ, Cohen SN et al. The chaplins: a family of hydrophobic cell-surface proteins involved in aerial mycelium formation in Streptomyces coelicolor. Genes Dev 2003; 17:1727–1740 [View Article][PubMed]
    [Google Scholar]
  25. Capstick DS, Willey JM, Buttner MJ, Elliot MA. SapB and the chaplins: connections between morphogenetic proteins in Streptomyces coelicolor. Mol Microbiol 2007; 64:602–613 [View Article]
    [Google Scholar]
  26. Holmes NA, Walshaw J, Leggett RM, Thibessard A, Dalton KA et al. Coiled-coil protein Scy is a key component of a multiprotein assembly controlling polarized growth in Streptomyces. Proc Natl Acad Sci USA 2013; 110:E397E406 [View Article][PubMed]
    [Google Scholar]
  27. Schwedock J, Mccormick JR, Angert ER, Nodwell JR, Losick R. Assembly of the cell division protein FtsZ into ladder-like structures in the aerial hyphae of Streptomyces coelicolor; 1997; 25847–858
  28. Kois A, Swiatek M, Jakimowicz D, Zakrzewska-Czerwińska J. SMC protein-dependent chromosome condensation during aerial hyphal development in Streptomyces. J Bacteriol 2009; 191:310–319 [View Article][PubMed]
    [Google Scholar]
  29. Davis NK, Chater KF. The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol Gen Genet 1992; 232:351–358[PubMed]
    [Google Scholar]
  30. Bursy J, Kuhlmann AU, Pittelkow M, Hartmann H, Jebbar M et al. Synthesis and uptake of the compatible solutes ectoine and 5-hydroxyectoine by Streptomyces coelicolor A3(2) in response to salt and heat stresses. Appl Environ Microbiol 2008; 74:7286–7296 [View Article][PubMed]
    [Google Scholar]
  31. Som NF, Heine D, Munnoch JT, Holmes NA, Knowles F et al. MtrA is an essential regulator that coordinates antibiotic production and sporulation in Streptomyces species. bioRxiv 2016
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000524
Loading
/content/journal/micro/10.1099/mic.0.000524
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Supplementary File 2

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error