Role of Divalent Ions in Membrane Models of Polymyxin-Sensitive and Resistant Gram-Negative Bacteria

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Publikace nespadá pod Fakultu sociálních studií, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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SAVENKO Mariia VÁCHA Robert RAMSEYER Christophe RIVEL Timothée Emmanuel Jonathan

Rok publikování 2025
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Chemical Information and Modeling
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://pubs.acs.org/doi/10.1021/acs.jcim.4c01574
Doi http://dx.doi.org/10.1021/acs.jcim.4c01574
Klíčová slova COLI OUTER-MEMBRANE; MOLECULAR-DYNAMICS; E.-COLI; ACINETOBACTER-BAUMANNII; SALMONELLA-TYPHIMURIUM; LIPOPOLYSACCHARIDE STRUCTURE; ESCHERICHIA-COLI; SOFTWARE NEWS; LIPID-A; BINDING
Přiložené soubory
Popis Polymyxins, critical last-resort antibiotics, impact the distribution of membrane-bound divalent cations in the outer membrane of Gram-negative bacteria. We employed atomistic molecular dynamics simulations to model the effect of displacing these ions. Two polymyxin-sensitive and two polymyxin-resistant models of the outer membrane of Salmonella enterica were investigated. First, we found that the removal of all calcium ions induces global stress on the model membranes, leading to substantial membrane restructuring. Next, we used enhanced sampling methods to explore the effects of localized stress by displacing membrane-bound ions. Our findings indicate that creating defects in the membrane-bound ion network facilitates polymyxin permeation. Additionally, our study of polymyxin-resistant mutations revealed that divalent ions in resistant model membranes are less likely to be displaced, potentially contributing to the increased resistance associated with these mutations. Lastly, we compared results from all-atom molecular dynamics simulations with coarse-grained simulations, demonstrating that the choice of force field significantly influences the behavior of membrane-bound ions under stress.
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