Fig. 10

Proposed mechanism of action of TP359. The proposed mechanism of action involves the interaction of the cationic TP359 with the outer membrane of P. aeruginosa, which is negatively charged due to lipopolysaccharide (LPS), causing membrane permeabilization and depolarization. This causes pores on the membrane resulting in efflux of cytoplasmic content to produce ghost cells. Furthermore, TP359 also caused down-regulation of outer membrane associated genes such as the acpP, oprL, oprI and most importantly the oprF. The protein products, AcpP, OprL, OprI and OprF are essential for fatty acid biosynthesis, transport of small molecules and structural membrane integrity. The effect of TP359 on the oprF gene may disrupt its product, the OprF, which encodes membrane integrity and structure, leading to a compromised membrane and ultimately cell death