TL;DR: The secondary metabolites manoalide, manoAlide monoacetate, and secomanoalide isolated from the sponge showed strong QS inhibition of a lasB::gfp(ASV) fusion, demonstrating the potential for further identification of specific QS antagonists from marine organisms.
Abstract: With the global emergence of multiresistant bacteria there is an increasing demand for development of new treatments to combat pathogens. Bacterial cell–cell communication [quorum sensing (QS)] regulates expression of virulence factors in a number of bacterial pathogens and is a new promising target for the control of infectious bacteria. We present the results of screening of 284 extracts of marine organisms from the Great Barrier Reef, Australia, for their inhibition of QS. Of the 284 extracts, 64 (23%) were active in a general, LuxR-derived QS screen, and of these 36 (56%) were also active in a specific Pseudomonas aeruginosa QS screen. Extracts of the marine sponge Luffariella variabilis proved active in both systems. The secondary metabolites manoalide, manoalide monoacetate, and secomanoalide isolated from the sponge showed strong QS inhibition of a lasB::gfp(ASV) fusion, demonstrating the potential for further identification of specific QS antagonists from marine organisms.
TL;DR: Surprisingly, the cobra venom phospholipase normally acts poorly on phosphatidylethanolamine as substrate, but after reaction with manoalide, the enzyme is somewhat more active toward this substrate rather than being inhibited, which suggests that a lysine residue may be important in understanding the substrate specificity of phosphate A2.
TL;DR: A kinetic plot of initial velocity versus [PLA2] supported the hypothesis that MLD apparently inactivates bee venom PLA2 by an irreversible mechanism.
TL;DR: There may be important differences between the intracellular P388D1 PLA2 and the more commonly studied extracellular forms of PLA2, and the need for the evaluation of inhibitors both in vitro and in vivo using the isolated enzyme and intact cell is emphasized.
TL;DR: The role of phospholipases in cellular activation and arachidonic acid production for prostaglandin and leukotriene biosynthesis is reviewed, and the “dualospholipid model” for phospholIPase A2 action at the lipid/water interface is described in detail.
Abstract: The role of phospholipases in cellular activation and arachidonic acid production for prostaglandin and leukotriene biosynthesis is reviewed. Particular emphasis is placed on the function of phospholipase A2 in the processes. The experimental basis of our current state of knowledge of the mechanism of action of the pure, extracellular phospholipase A2 is considered in detail. Experimental approaches dealing with lipid activation, surface dilution kinetics, and enzyme aggregation are considered, and the “dual phospholipid model” for phospholipase A2 action at the lipid/water interface is described in detail. The kinetic analysis of phospholipase A2 inhibitors, including p-bromophenacylbromide, manoalide, and an alkylether amide analogue of phosphatidylcholine, is considered in light of this model.