Autoinducer-2-based chemical communication in bacteria: complexities of interspecies signaling

Abstract

Cell-cell communication in bacteria, called quorum sensing, relies on production, release, and detection of signaling molecules, termed autoinducers. Communication enables populations of cells to synchronize gene expression and therefore behave as a group in a manner akin to cells in multicellular organisms. Most quorum-sensing systems allow communication within an individual species of bacteria. However, one autoinducer, called AI-2, is produced and recognized by many different bacterial species, indicating that some bacteria communicate across species boundaries. Current studies are aimed at discovering the role that AI-2 plays in gene regulation. Differential gene expression in response to AI-2 may cause bacterial behavioral changes, such as biofilm formation or transition to a pathogenic state. Interestingly, multiple mechanisms to detect AI-2 exist. These differences likely reflect variations in the role that AI-2 plays for different bacteria. Additionally, structural analyses of the AI-2 receptor in V. harveyi have provided insight into bacterial trans-membrane signal transduction. A further understanding of bacterial quorum-sensing processes may facilitate development of new technologies aimed at interfering with bacterial communication and virulence.

Fig. 1

Quorum-sensing signaling networks. Low cell density (left sides of panels), High cell density (right sides of panels). a A LuxI/LuxR quorum-sensing circuit. The LuxI enzyme produces an AHL molecule that diffuses into the surroundings. At high cell densities, the LuxR protein binds the AHL and subsequently binds to DNA promoting the transcription of genes X and Y. b V. harveyi AI-1- and AI-2-dependent circuits. At low cell density, LuxN and LuxQ exist in kinase mode autophosphorylating at histidine (H1) and aspartic acid (D1) residues. Phosphate is passed to LuxU at the histidine (H2) site, and then to LuxO at an aspartic acid (D2). LuxO-P, with sigma factor σ⁵⁴, activates transcription of the sRNA genes. The sRNAs, with the RNA chaperone Hfq repress luxR expression. At high cell densities, AI-1 binds LuxN and AI-2 binds LuxP-LuxQ. Binding of autoinducers causes LuxN and LuxQ to switch to phosphatase mode. Phosphate is drained from LuxU and LuxO, terminating expression of the sRNA genes. LuxR is derepressed, and luciferase is expressed. c The E. coli and S. typhimurium Lsr system. At low cell densities, LsrR binds to DNA and represses expression of the lsr operon. At high cell densities, AI-2 is imported via the Lsr transporter and is phosphorylated by LsrK. AI-2-phosphate binds to LsrR causing it to release DNA, thus derepressing lsr transcription [adapted from 8, 28].

Fig. 2

Reactive methyl cycle and production of DPD. SAM-dependent methyltransferases convert SAM to SAH, accumulation of which confers product-feedback inhibition on methyltransferase reactions. SAH is detoxified to SRH by Pfs. SRH is converted to homocysteine and DPD by LuxS. Homocysteine can be recycled to SAM via MetH, which generates methionine, and MetK.

Fig. 3

Interconverting forms of DPD. Cyclization of DPD generates two major stereoisomers S-DHMF and R-DHMF. Hydration in aqueous solution forms S-THMF and R-THMF. S-THMF is able to complex with borate, forming S-THMF-borate [adapted from 11].

Fig. 4

Model for AI-2 dependent LuxPQ receptor activity. The top panels display the LuxPQ_p receptor complex from a ‘top-down’ view, and the lower panels are a 90° rotation, showing the complex from the side. In the absence of AI-2 (left) LuxQ-LuxQ9 dimers exist in a symmetric orientation both in the periplasm and the cytoplasm, and therefore are in kinase mode. AI-2 binding to LuxP (right) causes a conformational change in LuxP, and induces interactions with LuxQ9. Simultaneous contacts of LuxP with LuxQ and LuxQ9 rotates the complex into an asymmetric orientation. Rotation of the periplasmic domains is conferred to the cytoplasmic domains, switching LuxQ from kinase to phosphatase mode [figure 4 reproduced with permission, 28].