The effects of a novel Clostridium difficile quorum sensing molecule on growth and virulence factor production in Staphylococcus aureus

S. aureus infections range from minor skin diseases to life-threatening invasive infections, with treatments for all infections becoming increasingly difficult as a result of rising rates of antibiotic resistance and a paucity of novel antibiotics. As no S. aureus vaccines currently exist nor are likely to be developed in the near future, development of novel therapies is warranted. One potential option is the exploitation of bacterial quorum sensing systems to manipulate virulence factor production and growth. Since significant similarities exist between the quorum sensing systems of C. difficile and S. aureus, we investigated the effect of a recently described a quorum-sensing molecule (TI) that induces Clostridium difficile toxin production on S. aureus growth and virulence. The results demonstrated that TI affects S. aureus strains in a dose-dependent fashion, causes up- and down-regulation of numerous genes, including down regulation of many secreted toxins, and produces a dose-dependent biphasic effect in the production of excreted toxins LukS-PV and Hla in a manner independent of bacterial growth. There was no observable effect on biofilm production. These data suggest that the TI could potentially be exploited for the development of antibiotic independent S. aureus treatment strategies