Crowd control: quorum sensing in Enterococcus

Abstract

Cytolysin, an important virulence factor for the opportunistic pathogen Enterococcus faecalis, can target bacteria and mammalian cells. The synthesis of this toxin is elaborate, involving post-translational modification, proteolytic cleavage, secretion and an additional step of extracellular proteolytic degradation of two subunits to produce the mature cytolysin. This complexity and an additional gene product are responsible for protecting cytolysin-producing bacteria. Although its synthesis has been well studied, until now the regulation of toxin production was unknown.Haas et al. [1xTwo-component regulator of Enterococcus faecalis cytolysin responds to quorum-sensing autoinduction. Haas, W. et al. Nature. 2002; 415: 84–87CrossRef | PubMed | Scopus (131)See all References][1] noticed that expression from the promoter of the cytolysin structural genes was repressed in the presence of two regulators, CylR1 and CylR2, the genes for which are located upstream from, and orientated in the opposite direction to, this promoter. The motifs present in these regulatory proteins suggest their function: CylR1 has three membrane-spanning regions, and so is probably a membrane detector, whereas CylR2 has a DNA-binding region, presumably for binding a promoter. Together, these regulators are implicated in repressing the expression of the cytolysin structural genes. The signal for the derepression was found to be one of the fully mature cytolysin subunits, CylLs′′. Addition of the culture supernatants containing only CylLs′′ induced transcription of the structural genes for both cytolysin subunits, but not the regulatory genes. This transcriptional activity was dependent on the amount of CylLs′′ added, suggesting that at a certain bacterial cell density the accumulation of this factor induces additional expression of the cytolysin structural genes.This mechanism of density-dependent activation represents a type of ‘quorum sensing’ that is distinct from those currently known in Gram-negative bacteria or other Gram-positive bacteria in terms of the signal, the detector and the mechanism of activation. This newly recognized system of cell–cell communication could provide good targets for inhibition of virulence factor expression. Finding such inhibitors is of crucial importance as Enterococcus is one of the main causes of antibiotic-resistant nosocomial infections.