Interspecies communication in bacteria

Abstract

Until recently, bacteria were considered to live rather asocial, reclusive lives. New research shows that, in fact, bacteria have elaborate chemical signaling systems that enable them to communicate within and between species. One signal, termed AI-2, appears to be universal and facilitates interspecies communication. Many processes, including virulence factor production, biofilm formation, and motility, are controlled by AI-2. Strategies that interfere with communication in bacteria are being explored in the biotechnology industry with the aim of developing novel antimicrobials. AI-2 is a particularly attractive candidate for such studies because of its widespread use in the microbial kingdom.

Figure 1

Three canonical quorum-sensing circuits in bacteria. (a) In Gram-negative bacteria, AHLs (red triangles) are produced by LuxI-like proteins and are detected by LuxR-type proteins. AHLs freely diffuse across the cell membrane and increase in concentration in the environment in proportion to cell growth. LuxR-type proteins, when bound to cognate autoinducers, bind specific promoter DNA elements and activate transcription of target genes (xyz). (b) Gram-positive bacteria synthesize oligopeptides (red wavy lines) that are typically modified at specific amino acids and are actively secreted. Detection occurs via a two-component signal transduction circuit, leading to the phosphorylation of a response regulator protein, which can bind promoter DNA and regulate transcription of target genes (xyz). (c) Quorum sensing in Vibrio harveyi. Two parallel two-component systems detect AI-1 (blue triangles), an AHL synthesized by LuxLM, and AI-2 (red circles), a furanosyl borate diester, which is synthesized by LuxS. In the absence of autoinducer, the sensors act as kinases and autophosphorylate at a conserved histidine residue, H1, and the phosphate is transferred to a conserved aspartate residue, D1, in the response regulator domain. Phosphate is sequentially transferred to the conserved histidine (H2) of the phosphotransferase LuxU and then to the conserved aspartate (D2) of the response regulator LuxO. Phospho-LuxO indirectly represses transcription of luxCDABE, the enzymes encoding luciferase. Binding of the autoinducers by LuxN and LuxPQ leads to the dephosphorylation of LuxU and LuxO. Dephosphorylation of LuxO relieves repression of luxCDABE. A transcriptional activator called LuxR (not similar to LuxR in a) is required for expression of luxCDABE.

Figure 2

Structures of different bacterial autoinducers. (a) Examples of AHL autoinducers of some Gram-negative bacteria. (b) A selection of Gram-positive AIP autoinducers. The asterisk above the tryptophan (W) of ComX indicates a posttranslational isoprenylation of the peptide. The AIP molecules of Staphylococcus aureus are shown with the thioester bridge linking the indicated amino acid residues. The numbering I–IV refers to the S. aureus group classification. (c) AI-2 of Vibrio harveyi is a furanosyl borate diester, as determined by co-crystallization with the V. harveyi AI-2 receptor LuxP.

Figure 3

Modular organization of two-component signal transduction cascades in bacteria. Bacteria typically detect changes in their environment using two-component phosphorelay systems. Information is detected by the first protein component, which is usually a membrane-spanning sensor-histidine kinase (green). Phosphate is transferred to the response regulator protein that is responsible for controlling the output (red). The sensor protein is autophosphorylated on a conserved histidine residue (H1). Phosphate is transferred to a conserved aspartate residue (D1) on the response regulator. Two-component systems often include additional response regulator and phosphotransferase proteins (blue and yellow domains, respectively) that contain conserved aspartate and histidine residues. The modular domain organization of the two-component circuits can vary, as these circuits can be composed of two, three, or four protein partners.

Figure 4

Biosynthesis of AI-2. Utilization of SAM as a methyl donor in cellular processes yields S-adenosylhomocysteine (SAH). The enzyme Pfs converts SAH to S-ribosylhomocysteine (SRH). LuxS is responsible for the conversion of SRH to homocysteine and DPD. DPD is predicted to spontaneously rearrange into various furanones. The furanone predicted to lead to the formation of V. harveyi AI-2 is the only one shown and is termed pro–AI-2. Borate adds to pro–AI-2 to form the active signaling molecule AI-2.