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

• DOI: 10.1021/acs.jcim.4c01574
• Publication Date: 2025-01-18T13:59:54Z
• Authors: Mariia Savenko; Robert Vácha; Christophe Ramseyer; Timothée Rivel
• Keywords: Polymyxin; Divalent; Polymyxin B

Polymyxins, critical last-resort antibiotics, impact the distribution of membrane-bound divalent cations in outer membrane Gram-negative bacteria. We employed atomistic molecular dynamics simulations to model effect displacing these ions. Two polymyxin-sensitive and two polymyxin-resistant models Salmonella enterica were investigated. First, we found that removal all calcium ions induces global stress on membranes, leading substantial restructuring. Next, used enhanced sampling methods explore effects localized by Our findings indicate creating defects ion network facilitates polymyxin permeation. Additionally, our study mutations revealed resistant membranes are less likely be displaced, potentially contributing increased resistance associated with mutations. Lastly, compared results from all-atom coarse-grained simulations, demonstrating choice force field significantly influences behavior under stress.