Bacterial small-molecule signaling pathways

Abstract

Bacteria use diverse small molecules for extra- and intracellular signaling. They scan small-molecule mixtures to access information about both their extracellular environment and their intracellular physiological status, and based on this information, they continuously interpret their circumstances and react rapidly to changes. Bacteria must integrate extra- and intracellular signaling information to mount appropriate responses to changes in their environment. We review recent research into two fundamental bacterial small-molecule signaling pathways: extracellular quorum-sensing signaling and intracellular cyclic dinucleotide signaling. We suggest how these two pathways may converge to control complex processes including multicellularity, biofilm formation, and virulence. We also outline new questions that have arisen from recent studies in these fields.

Fig. 1

Small-molecule bacterial signals. Representative structures of autoinducer molecules used in bacterial cell-cell communication, and of the intracellular signaling molecule cdiGMP. The asterisk on the tryptophan residue of the Bacillus subtilis oligopeptide autoinducer represents an isoprenyl modification.

Fig. 2

AI-2: an interconverting family of extracellular signal molecules. The precursor molecule, DPD, undergoes various rearrangements and additional reactions to form distinct biologically active AI-2 signal molecules. The Vibrio harveyi AI-2 (S-THMF-borate) is produced by the upper pathway, and the Salmonella enterica serovar Typhimurium AI-2 (R-THMF) is produced by the lower pathway (13, 14).

Fig. 3

Possible convergence of quorum sensing and cdiGMP signaling in the regulation of diverse bacterial behaviors. Cell density–dependent extracellular autoinducers activate membrane-bound (shown) or cytoplasmic sensory receptor proteins (not shown) which, through DNA binding proteins, regulate cellular processes including those listed. A variety of extracellular signals activate membrane-bound (shown) or cytoplasmic DGC and PDEA domain proteins (not shown), which synthesize and hydrolyze cdiGMP, respectively. cdiGMP functions as an activator or repressor of many of the same cellular processes regulated by quorum signaling (listed). Hypothetical connections between quorum-sensing and cdiGMP signaling are denoted by dashed lines.