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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00617136" target="_blank" >RIV/61388963:_____/25:00617136 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/25:00140658

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jcim.4c01574" target="_blank" >https://doi.org/10.1021/acs.jcim.4c01574</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.4c01574" target="_blank" >10.1021/acs.jcim.4c01574</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Svazek periodika

65

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

1476-1491

Kód UT WoS článku

001399600300001

EID výsledku v databázi Scopus

2-s2.0-85215683240