New signal molecules on the quorum-sensing block

Abstract

Apart from AHLs and PQS, P. aeruginosa has recently been shown to produce another family of small diffusible signal molecules, the diketopiperazines (DKPs)5xQuorum-sensing crosstalk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria. Holden, M.T. et al. Mol. Microbiol. 1999; 33: 1254–1266Crossref | PubMed | Scopus (306)See all References5. These cyclic dipeptides were identified as a consequence of their ability to activate biosensors previously considered specific for AHLs. Although the DKPs are structurally quite distinct (Fig. 1Fig. 1), at high concentrations they are able to cross-activate AHL-dependent reporter constructs based on several different LuxR homologues5xQuorum-sensing crosstalk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria. Holden, M.T. et al. Mol. Microbiol. 1999; 33: 1254–1266Crossref | PubMed | Scopus (306)See all References5. The detection of these DKPs appears to be an example of fortuitous chemical crosstalk and raises the obvious question as to their origin and biological function(s). In higher plants and animals, DKPs exhibit a remarkable spectrum of biological and pharmacological activities9xBioactive cyclic dipeptides. Prasad, C. Peptides. 1995; 16: 151–164Crossref | PubMed | Scopus (222)See all References9. Therefore, although it is quite feasible that the DKPs do not function as bacteria-to-bacteria signalling molecules per se, they might have a role in modulating prokaryotic–eukaryotic interactions. In this respect, it is worth noting that certain AHLs possess potent immunomodulatory10xThe Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-l-homoserine lactone has immunomodulatory activity. Telford, G. et al. Infect. Immun. 1998; 66: 36–42PubMedSee all References10 and cardiovascular activity11xThe Pseudomonas aeruginosa quorum-sensing signal molecule, N-(3-oxododecanoyl)-l-homoserine lactone, inhibits porcine arterial smooth muscle contraction. Lawrence, R.N. et al. Br. J. Pharmacol. 1999; 128: 845–848Crossref | PubMed | Scopus (56)See all References11.In bacteria, the production of DKPs is not limited to P. aeruginosa, as other Gram-negative bacteria, including E. coli, produce the same or related molecules5xQuorum-sensing crosstalk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria. Holden, M.T. et al. Mol. Microbiol. 1999; 33: 1254–1266Crossref | PubMed | Scopus (306)See all References5. Moreover, for both Salmonella spp. and E. coli there are several reports of quorum-sensing-type phenomena3xQuorum sensing in Escherichia coli, Salmonella typhimurium and Vibrio harveyi: a new family of genes responsible for autoinducer production. Surette, M.G. et al. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 1639–1644Crossref | PubMed | Scopus (588)See all References, 12xQuorum-sensing acts at initiation of chromosomal replication in Escherichia coli. Withers, H.L. and Nordstrom, K. Proc. Natl. Acad. Sci. U. S. A. 1999; 95: 15694–15699Crossref | Scopus (61)See all References, 13xEscherichia coli genes regulated by cell-to-cell signalling. Baca-DeLancey, R.R. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 96: 4610–4614Crossref | Scopus (88)See all References, 14xStimulation of bacterial growth by heat-stable, norepinephrine-induced autoinducers. Freestone, P.P. et al. FEMS Microbiol. Lett. 1999; 172: 53–60Crossref | PubMedSee all References in which the structure(s) of the signal molecules(s) involved has yet to be elucidated. Such molecules may well prove to be DKPs or 4-quinolones.