Conserved virulence-control in Gram-positive bacteria?

Abstract

The accessory gene regulator (agr) locus is the major regulator of virulence-factor gene expression in staphylococci, and controls the upregulation of multiple extracellular proteins including toxins and proteases. The agr locus is autoinduced by a quorum sensing mechanism: it encodes a peptide pheromone that is secreted by the bacterial cell, and, once extracellular levels accumulate to a threshold level (quorum), they are detected by the agr signal transduction system, activating the gene regulation response. Because peptides produced by different staphylococcal species and subspecies inhibit the signal transduction step, such inhibitory peptides are proposed adjuncts to antibacterial therapy, and can be administered in vivo to reduce disease.Now, Qin and colleagues1xEffects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Qin, X. et al. Infect. Immun. 2000; 68: 2579–2586Crossref | PubMed | Scopus (201)See all References1 have reported that a similar mechanism for controlling virulence factor expression is present in Enterococcus faecalis, an important cause of hospital acquired infection. The E. faecalis regulator (fsr) locus is highly homologous to agr, it is autoregulated, and controls the upregulation of the exoproteins gelatinase and serine protease. Importantly, fsr mutants are attenuated in virulence. Although there is still much to do, this discovery suggests that similar signal transduction systems to agr might be widespread in pathogenic Gram-positive bacteria. These organisms are particularly difficult to treat in hospitals, because of their resistance to multiple antibiotics, so adjunct therapies that impact on virulence might be particularly useful. Whether a broad spectrum approach to encompass all Gram-positive bacteria can be developed awaits further characterization of this locus and investigation of other pathogens.