"Quorum sensing" and the regulation of bacterial virulence by small pheromones.

It is now clear that many bacterial plant and animal pathogens modulate the production of their virulence factors in response to cell population density - "quorum sensing". In fact, there is now a growing list of phenotypic traits (including virulence, carbapenem antibiotic production, enzyme synthesis, secondary metabolite synthesis etc.) which are under cell density-dependent control in various bacteria. The chemical communication signals used in this general density-dependent global regulation system are various N-acylated homoserine lactones (N-AHLs).

Fig 1: N-(3-oxohexanoyl)-L- homoserine lactone (OHHL)

These molecules are diffusible products made from the action of a putative enzyme which is homologous to the LuxI protein of Vibrio (or Photobacterium) fischeri - a bioluminescent marine bacterium. LuxI homologues are widespread in bacteria, as are homologues of LuxR, the transcriptional activator of the Vibrio bioluminescence operon. The N-AHLs are thought to bind to the LuxR homologues thereby enabling their function as transcriptional regulators. We are currently investigating multiple aspects of quorum sensing in the bacterial pathogen, Erwinia, where an N-AHL regulates production of multiple exoenzymes, virulence and an antibiotic (Fig 2).

Fig 2: Cross-feeding of OHHL between carbapenem-non-producing strains of Erwinia carotovora. The carR and carI strains of E. carotovora cannot respond to, or produce, N-(3-oxohexanoyl)-L-homoserine lactone, respectively. However, when the carR strain, which still produces the diffusible OHHL, is grown alongside the carI strain, carbapenem production is restored in the latter strain. The presence of the antibiotic is indicated by a zone of clearing in the lawn of a beta-lactam supersensitive strain of Escherichia coli.

DNA sequence information concerning the carI gene of Erwinia carotovora subsp. carotovora and the echI gene of Erwinia chrysanthemi has been lodged with GenBank under the accession numbers:

• X74299 - E. carotovora
• U45854 - E. chrysanthemi

Further information concerning the protein families involved in quorum sensing is held at ExPASy:

• CarI is a member of the autoinducer synthetase family of proteins.
• CarR is a member of the LuxR family of transcriptional activators.
• Links to the various CarI homologues and to the CarR/LuxR homologues.

Research in this area is also being carried out by the Quorum Sensing Group at Nottingham University

Page updated 31st October 2005

Pages maintained by Anne Barnard