Molecular Dynamics Simulations of Complex Bacterial Membranes

Abstract

Bacterial envelopes are a frontier that must be faced by all products that come into contact with them, including antibiotics, antiseptics and host defences. Many antimicrobials exploit features of the bacterial envelope in order to inhibit bacterial growth or cause cell death whilst the immune system recognises bacterial cell envelope patterns in order to mount an appropriate response. Given this, and the ever-growing concerns around antimicrobial resistance, it is vital that the mechanisms involved are well understood. This work used atomistic and coarse-grained molecular dynamics simulations to better understand the relationship between bacterial membranes and antimicrobials. The first chapter explored many of the aspects of the mode of action of membrane penetrating antibiotic, daptomycin. This investigated the relationship between daptomycin and calcium ions in addition to its dependence on phosphatidylglycerol. The second chapter of this work aimed to understand the mode of action of the membrane active antiseptic, chlorhexidine, on the Staphylococcus aureus membrane. The third chapter aimed to compare the differences of simulating chlorhexidine with the S. aureus membrane using different force fields. The final chapter focused on coarse- grain simulations of thrombin-derived C-terminal peptides (TCPs) with bacterial envelope products. This work aimed to support experimental work that had showed the co-aggregation of TCPs in the presence of bacterial envelope products as a mechanism to avoid host immune overreaction.

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Identifiers

ORCID for Syma Khalid: orcid.org/0000-0002-3694-5044

ORCID for Jonathan Essex: orcid.org/0000-0003-2639-2746

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