Bacterial signal transduction network in a genomic perspective^†

Abstract

SummaryBacterial signalling network includes an array of numerous interacting components that monitor environmental and intracellular parameters and effect cellular response to changes in these parameters. The complexity of bacterial signalling systems makes comparative genome analysis a particularly valuable tool for their studies. Comparative studies revealed certain general trends in the organization of diverse signalling systems. These include (i) modular structure of signalling proteins; (ii) common organization of signalling components with the flow of information from N-terminal sensory domains to the C-terminal transmitter or signal output domains (N-to-C flow); (iii) use of common conserved sensory domains by different membrane receptors; (iv) ability of some organisms to respond to one environmental signal by activating several regulatory circuits; (v) abundance of intracellular signalling proteins, typically consisting of a PAS or GAF sensor domains and various output domains; (vi) importance of secondary messengers, cAMP and cyclic diguanylate; and (vii) crosstalk between components of different signalling pathways. Experimental characterization of the novel domains and domain combinations would be needed for achieving a better understanding of the mechanisms of signalling response and the intracellular hierarchy of different signalling pathways.

Bacterial c-di-GMP Is an Immunostimulatory Molecule

“…The cyclic dinucleotide c-di-GMP is now recognized as a widespread intracellular signaling molecule in prokaryotes (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). We have explored the extracellular biological effects of c-di-GMP and its potential use as a therapeutic agent.…”

“…The level of intracellular c-di-GMP in some species is believed to be regulated by the opposing effects of diguanylate cyclases for c-di-GMP synthesis from GTP and c-di-GMP phosphodiesterase for breakdown to 5Ј-GMP and each controlling the level of c-di-GMP in the cell. c-di-GMP has been shown to influence bacterial cell survival, cell differentiation, colonization and biofilm formation, as well as bacteria-host interactions (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Although the role of intracellular c-di-GMP in bacteria is now recognized and is becoming an intense field of research, we have been studying the effect of this microbial molecule in the context of other biological systems and its potential clinical and therapeutic use for the prevention and inhibition of infection and disease (19 -22).…”

Novel σ B regulation modules of Gram-positive bacteria involve the use of complex hybrid histidine kinases

“…2), including CHASE3, GAF and PAS/PAC domains, of which the latter two have been implicated in small ligand/ cyclic nucleotide binding and redox/light/metabolite sensing, respectively (Galperin, 2004). The GAF sensory domain was highly conserved in the RsbK homologues and was always found next to, and N-terminally from, the HK phosphotransferase domain.…”

Shewanella oneidensis MR-1 Sensory Box Protein Involved in Aerobic and Anoxic Growth

“…The two domains are thought to interact with cyclic-diguanosine monophosphate (c-di-GMP), and c-di-GMP was recently proposed to be a global secondary messenger involved in regulating cell-cell and cell-surface interactions (9). The GGDEF domain was recently shown to be associated with the synthesis of c-di-GMP via diguanylate cyclase (DGC) and the EAL domain to contain phosphodiesterase (PDE) activity in Yersinia, Caulobacter, and Salmonella (9,16,27,24,38) and more recently in Shewanella (54). In addition, the involvement of DGC and PDE domains in cell metabolism and cell behavior has recently been shown in Burkholderia, Xanthomonas, Streptococcus, Vibrio, and Pseudomonas (for examples, see references 5 and 30).…”

“…In the postgenomic era, uncharacterized genes pose a major challenge in biology (16), and many sequenced genomes still contain a large fraction (up to 30 to 40%) of genes without defined physiological roles (13). In fact, many aspects of signaling and stress response most likely reside in this fraction of genes for a given organism and underlie the lack of understanding in physiological responses and control of metabolism.…”