Surfactants with their intrinsic ability to solubilize lipids are widely used as antibacterial agents. Interaction of surfactants with the bacterial cell envelope is complicated due to their propensity to aggregate. It is important to discern the interactions of micellar aggregates and single surfactants on the various components of the cell envelope to improve selectivity and augment the efficacy of surfactant-based products. In this study, we present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior kill efficacy of laurate over oleate observed in contact time assays with live <i>E. coli</i>. To gain a molecular understanding of these differences, we performed all-atom molecular dynamics simulations to observe the 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, thereby revealing an intrinsic sieving property of the bacterial cell wall to effectively modulate the surfactant concentration at the inner membrane. The molecular dynamics simulations exhibit greater 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. The novel molecular insights gained from our study uncovers hitherto unexplored pathways to rationalize the development of antimicrobial formulations and therapeutics.

Interactions of surfactants with the bacterial cell wall and inner membrane: Revealing the link between aggregation and antimicrobial activity

ACS Spring 2022

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