Sharma, P and Vaiwala, R and Parthasarathi, S and Patil, N and Verma, A and Waskar, M and Raut, JS and Basu, JK and Ayappa, KG (2022) Interactions of Surfactants with the Bacterial Cell Wall and Inner Membrane: Revealing the Link between Aggregation and Antimicrobial Activity. In: Langmuir, 38 (50). pp. 15714-15728.
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Abstract
Surfactants with their intrinsic ability to solubilize lipid membranes are widely used as antibacterial agents, and their interactions with the bacterial cell envelope are complicated by their differential aggregation tendencies. We present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior antimicrobial activity and faster kill kinetics of shorter-chain fatty acid surfactant, laurate, when compared with the longer-chain surfactants studied in contact time assays with live Escherichia coli (E. coli). From all-atom molecular dynamics simulations, translocation events across peptidoglycan were the highest for laurate followed by sodium dodecyl sulfate, myristate, palmitate, oleate, and stearate. The translocation kinetics were positively correlated with the critical micellar concentration, which determined the free monomer surfactant concentration available for translocation across peptidoglycan. Interestingly, aggregates showed a lower propensity to translocate across the peptidoglycan layer and longer translocation times were observed for oleate, thereby revealing an intrinsic sieving property of the bacterial cell wall. Molecular dynamics simulations with surfactant-incorporated bacterial inner membranes revealed the greatest hydrophobic mismatch and membrane thinning in the presence of laurate when compared with the other surfactants. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, and electroporation molecular dynamics simulations revealed greater inner membrane poration tendency in the presence of laurate when compared with the longer-chain surfactants. Our study provides molecular insights into surfactant translocation across peptidoglycan and chain length-induced structural disruption of the inner membrane, which correlate with contact time kill efficacies observed as a function of chain length with E. coli. The insights gained from our study uncover unexplored barrier properties of the bacterial cell envelope to rationalize the development of antimicrobial formulations and therapeutics. © 2022 American Chemical Society.
| Item Type: | Journal Article |
|---|---|
| Publication: | Langmuir |
| Publisher: | American Chemical Society |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | Cell membranes; Chain length; Cytology; Escherichia coli; Palmitic acid; Sodium dodecyl sulfate; Sulfur compounds, Anti-microbial activity; Bacterial cells; Cell envelopes; Cell walls; Contact time; Dynamics simulation; Inner membranes; Laurate; Long chains; Peptidoglycans, Molecular dynamics |
| Department/Centre: | Division of Mechanical Sciences > Chemical Engineering Division of Physical & Mathematical Sciences > Physics |
| Date Deposited: | 22 Jan 2023 06:46 |
| Last Modified: | 22 Jan 2023 06:46 |
| URI: | https://eprints.iisc.ac.in/id/eprint/79227 |
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