1887

Microbiology Society logo

Volume 159, Issue Pt_7

Cyclic di-GMP signalling and the regulation of bacterial virulence Free

Abstract

Signal transduction pathways involving the second messenger cyclic di-GMP [bis-(3′-5′)-cyclic di-guanosine monophosphate] occur widely in bacteria where they act to link perception of environmental or intracellular cues and signals to specific alterations in cellular function. Such alterations can contribute to bacterial lifestyle transitions including biofilm formation and virulence. The cellular levels of the nucleotide are controlled through the opposing activities of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). The GGDEF domain of DGCs catalyses the synthesis of cyclic di-GMP from GTP, whereas EAL or HD-GYP domains in different classes of PDE catalyse cyclic di-GMP degradation to pGpG and GMP. We are now beginning to understand how alterations in cyclic di-GMP exert a regulatory action through binding to diverse receptors or effectors that include a small ‘adaptor’ protein domain called PilZ, transcription factors and riboswitches. The regulatory action of enzymically active cyclic di-GMP signalling proteins is, however, not restricted to an influence on the level of nucleotide. Here, I will discuss our recent findings that highlight the role that protein–protein interactions involving these signalling proteins have in regulating functions that contribute to bacterial virulence.

  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.068189-0
2013-07-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/micro/159/7/1286.html?itemId=/content/journal/micro/10.1099/mic.0.068189-0&mimeType=html&fmt=ahah

References

  1. Abel S., Chien P., Wassmann P., Schirmer T., Kaever V., Laub M. T., Baker T. A., Jenal U.( 2011). Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks. Mol Cell 43:550–560 [View Article][PubMed]
     [Google Scholar]
  2. An S.-Q., Febrer M., McCarthy Y., Tang D.-J., Clissold L., Kaithakottil G., Swarbreck D., Tang J.-L., Rogers J. et al.( 2013). High-resolution transcriptional analysis of the regulatory influence of cell-to-cell signalling reveals novel genes that contribute to Xanthomonas phytopathogenesis. Mol Microbiol 88:1058–1069 [View Article][PubMed]
     [Google Scholar]
  3. Andrade M. O., Alegria M. C., Guzzo C. R., Docena C., Rosa M. C. P., Ramos C. H. I., Farah C. S.( 2006). The HD-GYP domain of RpfG mediates a direct linkage between the Rpf quorum-sensing pathway and a subset of diguanylate cyclase proteins in the phytopathogen Xanthomonas axonopodis pv citri. Mol Microbiol 62:537–551 [View Article][PubMed]
     [Google Scholar]
  4. Barber C. E., Tang J. L., Feng J. X., Pan M. Q., Wilson T. J., Slater H., Dow J. M., Williams P., Daniels M. J.( 1997). A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule. Mol Microbiol 24:555–566 [View Article][PubMed]
     [Google Scholar]
  5. Boyd C. D., O’Toole G. A.( 2012). Second messenger regulation of biofilm formation: breakthroughs in understanding c-di-GMP effector systems. Annu Rev Cell Dev Biol 28:439–462 [View Article][PubMed]
     [Google Scholar]
  6. Cheng Z., He Y. W., Lim S. C., Qamra R., Walsh M. A., Zhang L. H., Song H.( 2010). Structural basis of the sensor-synthase interaction in autoinduction of the quorum sensing signal DSF biosynthesis. Structure 18:1199–1209 [View Article][PubMed]
     [Google Scholar]
  7. Chin K. H., Lee Y. C., Tu Z. L., Chen C. H., Tseng Y. H., Yang J. M., Ryan R. P., McCarthy Y., Dow J. M. et al.( 2010). The cAMP receptor-like protein CLP is a novel c-di-GMP receptor linking cell-cell signaling to virulence gene expression in Xanthomonas campestris.. J Mol Biol 396:646–662 [View Article][PubMed]
     [Google Scholar]
  8. Christen M., Christen B., Folcher M., Schauerte A., Jenal U.( 2005). Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP. J Biol Chem 280:30829–30837 [View Article][PubMed]
     [Google Scholar]
  9. Chugani S., Greenberg E. P.( 2007). The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression. Microb Pathog 42:29–35 [View Article][PubMed]
     [Google Scholar]
  10. Dow J. M., Crossman L., Findlay K., He Y. Q., Feng J. X., Tang J. L.( 2003). Biofilm dispersal in Xanthomonas campestris is controlled by cell-cell signaling and is required for full virulence to plants. Proc Natl Acad Sci U S A 100:10995–11000 [View Article][PubMed]
     [Google Scholar]
  11. Galperin M. Y., Natale D. A., Aravind L., Koonin E. V.( 1999). A specialized version of the HD hydrolase domain implicated in signal transduction. J Mol Microbiol Biotechnol 1:303–305[PubMed]
     [Google Scholar]
  12. Galperin M. Y., Nikolskaya A. N., Koonin E. V.( 2001). Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol Lett 203:11–21 [View Article][PubMed]
     [Google Scholar]
  13. Hammer B. K., Bassler B. L.( 2009). Distinct sensory pathways in Vibrio cholerae El Tor and classical biotypes modulate cyclic dimeric GMP levels to control biofilm formation. J Bacteriol 191:169–177 [View Article][PubMed]
     [Google Scholar]
  14. He Y. W., Wang C., Zhou L., Song H., Dow J. M., Zhang L. H.( 2006). Dual signaling functions of the hybrid sensor kinase RpfC of Xanthomonas campestris involve either phosphorelay or receiver domain-protein interaction. J Biol Chem 281:33414–33421 [View Article][PubMed]
     [Google Scholar]
  15. Hengge R.( 2009). Principles of c-di-GMP signalling in bacteria. Nat Rev Microbiol 7:263–273 [View Article][PubMed]
     [Google Scholar]
  16. Ichikawa J. K., Norris A., Bangera M. G., Geiss G. K., van't Wout A. B., Bumgarner R. E., Lory S.( 2000). Interaction of Pseudomonas aeruginosa with epithelial cells: identification of differentially regulated genes by expression microarray analysis of human cDNAs. Proc Natl Acad Sci U S A 97:9659–9664 [View Article][PubMed]
     [Google Scholar]
  17. Leduc J. L., Roberts G. P.( 2009). Cyclic di-GMP allosterically inhibits the CRP-like protein (Clp) of Xanthomonas axonopodis pv. citri.. J Bacteriol 191:7121–7122 [View Article][PubMed]
     [Google Scholar]
  18. Lovering A. L., Capeness M. J., Lambert C., Hobley L., Sockett R. E.( 2011). The structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases. mBio 2:e00163-11 [View Article][PubMed]
     [Google Scholar]
  19. Lu X. H., An S. Q., Tang D. J., McCarthy Y., Tang J. L., Dow J. M., Ryan R. P.( 2012). RsmA regulates biofilm formation in Xanthomonas campestris through a regulatory network involving cyclic di-GMP and the Clp transcription factor. PLoS ONE 7:e52646 [View Article][PubMed]
     [Google Scholar]
  20. McCarthy Y., Ryan R. P., O'Donovan K., He Y.- Q., Jiang B.-L., Feng J.-X., Tang J.-L., Dow J. M.( 2008). The role of PilZ domain proteins in the virulence of Xanthomonas campestris pv. campestris. Mol Plant Pathol 9:819–826 [View Article][PubMed]
     [Google Scholar]
  21. Newell P. D., Boyd C. D., Sondermann H., O’Toole G. A.( 2011). A c-di-GMP effector system controls cell adhesion by inside-out signaling and surface protein cleavage. PLoS Biol 9:e1000587 [View Article][PubMed]
     [Google Scholar]
  22. Paul R., Weiser S., Amiot N. C., Chan C., Schirmer T., Giese B., Jenal U.( 2004). Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. Genes Dev 18:715–727 [View Article][PubMed]
     [Google Scholar]
  23. Römling U., Galperin M. Y., Gomelsky M.( 2013). Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev 77:1–52 [View Article][PubMed]
     [Google Scholar]
  24. Ross P., Weinhouse H., Aloni Y., Michaeli D., Weinberger-Ohana P., Mayer R., Braun S., de Vroom E., van der Marel G. A. et al.( 1987). Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325:279–281 [View Article][PubMed]
     [Google Scholar]
  25. Ryan R. P., Fouhy Y., Lucey J. F., Crossman L. C., Spiro S., He Y. W., Zhang L. H., Heeb S., Cámara M. et al.( 2006). Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. Proc Natl Acad Sci U S A 103:6712–6717 [View Article][PubMed]
     [Google Scholar]
  26. Ryan R. P., Fouhy Y., Lucey J. F., Jiang B. L., He Y. Q., Feng J. X., Tang J. L., Dow J. M.( 2007). Cyclic di-GMP signalling in the virulence and environmental adaptation of Xanthomonas campestris.. Mol Microbiol 63:429–442 [View Article][PubMed]
     [Google Scholar]
  27. Ryan R. P., Lucey J., O’Donovan K., McCarthy Y., Yang L., Tolker-Nielsen T., Dow J. M.( 2010). HD-GYP domain proteins regulate biofilm formation and virulence in Pseudomonas aeruginosa.. Environ Microbiol 11:1126–1136 [View Article][PubMed]
     [Google Scholar]
  28. Ryan R. P., McCarthy Y., Andrade M., Farah C. S., Armitage J. P., Dow J. M.( 2010). Cell-cell signal-dependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in Xanthomonas campestris.. Proc Natl Acad Sci USA 107:5989–5994 [View Article][PubMed]
     [Google Scholar]
  29. Ryan R. P., McCarthy Y., Kiely P. A., O’Connor R., Farah C. S., Armitage J. P., Dow J. M.( 2012a). Dynamic complex formation between HD-GYP, GGDEF and PilZ domain proteins regulates motility in Xanthomonas campestris.. Mol Microbiol 86:557–567 [View Article][PubMed]
     [Google Scholar]
  30. Ryan R. P., Tolker-Nielsen T., Dow J. M.( 2012b). When the PilZ don’t work: effectors for cyclic di-GMP action in bacteria. Trends Microbiol 20:235–242 [View Article][PubMed]
     [Google Scholar]
  31. Schirmer T., Jenal U.( 2009). Structural and mechanistic determinants of c-di-GMP signalling. Nat Rev Microbiol 7:724–735 [View Article][PubMed]
     [Google Scholar]
  32. Slater H., Alvarez-Morales A., Barber C. E., Daniels M. J., Dow J. M.( 2000). A two-component system involving an HD-GYP domain protein links cell-cell signalling to pathogenicity gene expression in Xanthomonas campestris.. Mol Microbiol 38:986–1003 [View Article][PubMed]
     [Google Scholar]
  33. Sondermann H., Shikuma N. J., Yildiz F. H.( 2012). You’ve come a long way: c-di-GMP signaling. Curr Opin Microbiol 15:140–146 [View Article][PubMed]
     [Google Scholar]
  34. Sultan S. Z., Pitzer J. E., Miller M. R., Motaleb M. A.( 2010). Analysis of a Borrelia burgdorferi phosphodiesterase demonstrates a role for cyclic-di-guanosine monophosphate in motility and virulence. Mol Microbiol 77:128–142 [View Article][PubMed]
     [Google Scholar]
  35. Sultan S. Z., Pitzer J. E., Boquoi T., Hobbs G., Miller M. R., Motaleb M. A.( 2011). Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi.. Infect Immun 79:3273–3283 [View Article][PubMed]
     [Google Scholar]
  36. Tang J. L., Liu Y. N., Barber C. E., Dow J. M., Wootton J. C., Daniels M. J.( 1991). Genetic and molecular analysis of a cluster of rpf genes involved in positive regulation of synthesis of extracellular enzymes and polysaccharide in Xanthomonas campestris pathovar campestris.. Mol Gen Genet 226:409–417 [View Article][PubMed]
     [Google Scholar]
  37. Tao F., He Y. W., Wu D. H., Swarup S., Zhang L. H.( 2010). The cyclic nucleotide monophosphate domain of Xanthomonas campestris global regulator Clp defines a new class of cyclic di-GMP effectors. J Bacteriol 192:1020–1029 [View Article][PubMed]
     [Google Scholar]
  38. Tischler A. D., Camilli A.( 2004). Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol Microbiol 53:857–869 [View Article][PubMed]
     [Google Scholar]
  39. Tschowri N., Busse S., Hengge R.( 2009). The BLUF-EAL protein YcgF acts as a direct anti-repressor in a blue-light response of Escherichia coli.. Genes Dev 23:522–534 [View Article][PubMed]
     [Google Scholar]
  40. Tschowri N., Lindenberg S., Hengge R.( 2012). Molecular function and potential evolution of the biofilm-modulating blue light-signalling pathway of Escherichia coli.. Mol Microbiol 85:893–906 [View Article][PubMed]
     [Google Scholar]
  41. Vojnov A. A., Slater H., Newman M. A., Daniels M. J., Dow J. M.( 2001). Regulation of the synthesis of cyclic glucan in Xanthomonas campestris by a diffusible signal molecule. Arch Microbiol 176:415–420 [View Article][PubMed]
     [Google Scholar]
  42. Wang L. H., He Y. W., Gao Y. F., Wu J. E., Dong Y. H., He C. Z., Wang S. X., Weng L. X., Xu J. L. et al.( 2004). A bacterial cell-cell communication signal with cross-kingdom structural analogues. Mol Microbiol 51:903–912 [View Article][PubMed]
     [Google Scholar]
  43. Wolfgang M. C., Jyot J., Goodman A. L., Ramphal R., Lory S.( 2004). Pseudomonas aeruginosa regulates flagellin expression as part of a global response to airway fluid from cystic fibrosis patients. Proc Natl Acad Sci U S A 101:6664–6668 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.068189-0
Loading
Cyclic di-GMP signalling and the regulation of bacterial virulence
Microbiology 159, 1286 (2013); https://doi.org/10.1099/mic.0.068189-0
/content/journal/micro/10.1099/mic.0.068189-0
/content/journal/micro/10.1099/mic.0.068189-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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