Role of novel quorum sensing molecules (DKPs-Diketopiperazines) as activators of bacterial virulence and host response

Objectives: The aim of this project was to establish the functional role of novel quorum sensing molecules (Diketopiperazines – DKPs) on activation of bacterial virulence properties and the potential effects on host cells as activators of the innate immune response. Methods: The effect of DKPs on the growth and virulence properties of the periodontal pathogen, Porphyromonas gingivalis (P.g.) A7436 strain was examined. Secondarily, the effect of DKPs on human monocyte (THP-1) viability, growth and cytokine production upon lipopolysaccharide (LPS) stimulation was determined. THP-1 cells were collected, counted and the cell lysate was evaluated for Interleukin 1β (IL-1β) mRNA expression. Results: Our results demonstrate that DKPs minimally affect the growth of P. g. DKP alone did not significantly alter THP-1 viability (p=0.20), indicating it was not toxic to the cells. However, analysis of the IL-1β mRNA expression indicates that DKP inhibited the inflammatory response of LPS-stimulated THP-1 cells. Conclusions: We have confirmed that DKPs minimally affect the growth of P. g. and cyclo(Leu-Pro) appears to slow the replication of THP-1 cells. Cyclo(Leu-Pro) seems to inhibit the expression of IL-1β in THP-1 cells.Master of Scienc