The role of sodium salicylate as a virulence inhibitor for soft tissue infections

Abstract

Approximately 2% of the total population will suffer from chronic wounds during their lifetime. These wounds can last for years and are associated with considerable patient suffering and large socioeconomic costs. Infection is considered an important factor for delayed healing. Due to the continued development of antibiotic resistance, novel alternative treatment strategies are urgently needed. Quorum sensing (QS), a signalling system used by important wound pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, regulates the production of virulence factors and is thus an attractive target.

The aim of this thesis was to evaluate the effect of sodium salicylate (NaSa) on P. aeruginosa and S. aureus QS activity and the production of virulence factors and how this influences the host immune response both in vitro and in vivo. Furthermore, a collection of P. aeruginosa chronic wound isolates was characterized in terms of QS signalling and virulence factor production. The results showed that approximately 50% of the clinical P. aeruginosa strains produced the majority of the investigated virulence factors and QS signals. In P. aeruginosa, NaSa reduced QS activity and the production of virulence factors, such as pyocyanin, pyoverdine, proteases and biofilm. In the presence of NaSa, P. aeruginosa formed smaller biofilm aggregates, which were more easily eradicated by silver. In S. aureus, the effect of NaSa on QS and virulence factor production was concentration dependent. Specifically, high levels of NaSa reduced QS and virulence production, whereas the opposite was observed for lower NaSa concentrations. In some instances, biofilm formation was induced by NaSa but without increasing its tolerance towards silver or antibiotics. In vitro, immune cells stimulated with supernatants from NaSa-treated P. aeruginosa cultures demonstrated increased migration and phagocytic capacity compared to untreated supernatants. In vivo, rats stimulated with NaSa-treated supernatants showed increased immune cell infiltration and reduced secretion of proinflammatory cytokines. In conclusion, NaSa influences QS and virulence factor production in P. aeruginosa and S. aureus, resulting in the stimulation of important immune functions in vitro and in vivo.