(442a) Interactions of Surfactants with the Bacterial Cell Wall and Inner Membrane: Revealing the Link between Aggregation and Antimicrobial Activity

Surfactants with their intrinsic ability to solubilize lipids are widely used as antibacterial agents, however their interactions with the bacterial cell envelope is complicated due to their propensity to aggregate and induce structural changes to the membrane. Discerning the interactions of micellar aggregates and single surfactants on the various components of the cell envelope will help improve antimicrobial efficacy and kinetics of surfactant-based products. We present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior antimicrobial activity and faster kill kinetics of laurate over oleate observed in contact time assays with live E. coli. From all-atom molecular dynamics simulations we investigated interactions of surfactants with the periplasmic peptidoglycan layer and the inner membrane of Gram-negative bacteria. The peptidoglycan layer allows a greater number of translocation events for laurate when compared with oleate molecules. More interestingly, aggregates did not translocate the peptidoglycan layer and longer translocation times were observed for oleate, thereby revealing an intrinsic sieving property of the bacterial cell wall to effectively modulate the surfactant concentration at the inner membrane. Molecular dynamics simulations exhibit increased thinning of the inner membrane in the presence of laurate when compared with oleate, and laurate induced greater disorder and decreased the bending modulus of the inner membrane to a greater extent. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, which revealed that laurate induced vesicle rupture at lower concentrations in contrast to oleate where gradual rupture events were also observed. The novel molecular insights gained from our study uncovers hitherto unexplored pathways to rationalize the development of antimicrobial formulations and therapeutics.