Interactions between polymyxin B and various bacterial membrane mimics: A molecular dynamics study

Sun, Yuliang; Deng, Zhi-Xiong; Jiang, Xukai; Yuan, Bing; Yang, Kai

doi:10.1016/j.colsurfb.2021.112288

Cited by 9 publications

(8 citation statements)

References 59 publications

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“…On the other hand, the free PMB tends to embed shallowly to the membrane ( Figure 5 c and Figure S3b ). These results are consistent with previous observations [ 10 , 45 ]. Moreover, after the embedding of GO or PMB, the membrane keeps intact without obvious disturbance of the bilayer structure.…”

Section: Resultssupporting

confidence: 94%

“…To give an insight into the underlying mechanism, MD simulations were performed to investigate the interaction process between agents and a bilayer membrane. Here, a well-established coarse-grained (CG) Martini force field was applied in the simulations [ 10 , 17 ]. It is found that the GO nanosheet tends to insert into the membrane quickly (within 2000 ns) and then be stably sandwiched between the two leaflets, whatever the initial orientations are (even when it is originally vertical to the membrane plane; Figure 5 b and Figure S3a ).…”

Section: Resultsmentioning

confidence: 99%

“…The coarse-grained (CG) model of PMB was obtained by using the Martinize script (Prof. dr. Siewert-Jan Marrink, University of Groningen, Groningen, Netherlands) with the crystal structure of peptide [ 10 , 31 , 32 ]. For GO nanosheets, the nanosheet was constructed by mapping 9 carbon atoms into 1 CG SC4 bead, and the beads within 1.2 nm were constrained by harmonic springs with a force constant of 12,000 kJ mol −1 nm −2 .…”

Section: Methodsmentioning

confidence: 99%

“…It is generally accepted that lipid A, the main constituent part of lipopolysaccharide (LPS) in the outer membrane (OM) of bacteria, is one of the action targets of PMB [ 8 , 9 ]. The adsorption and aggregation of PMBs on the OM surface disrupt the high surface charge density of the counter-crosslinked lipid A moieties due to DAB residues of the peptides, and consequently facilitate penetration of hydrophobic fatty acid tails into the membrane, leading to destabilization and permeabilization of the OM [ 5 , 8 , 10 ]. A similar disruption process of the inner membrane (IM) is also established, composed of the DAB-based adsorption followed by a rapid insertion of fatty acid tails into the bilayer.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B

Zhang

Sun

et al. 2022

Polymers

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Drug-resistant Gram-negative bacteria pose a serious threat to public health, and polymyxin B (PMB) is clinically used as a last-line therapy for the treatment of infections caused by these pathogens. However, the appearance of PMB resistance calls for an effort to develop new approaches to improve its antibacterial performance. In this work, a new type of nanocomposite, composed of PMB molecules being chemically decorated on the surface of graphene oxide (GO) nanosheets, was designed, which showed potent antibacterial ability through synergistically and physically disturbing the bacterial membrane. The as-fabricated PMB@GO nanocomposites demonstrated an enhanced bacterial-killing efficiency, with a minimum inhibitory concentration (MIC) value half of that of free PMB (with an MIC value as low as 0.5 μg mL−1 over Escherichia coli), and a bacterial viability less than one fourth of that of PMB (with a bacterial reduction of 60% after 3 h treatment, and 90% after 6 h incubation). Furthermore, the nanocomposite displayed moderate cytotoxicity or hemolysis effect, with cellular viabilities over 85% at concentrations up to 16 times the MIC value. Studies on antibacterial mechanism revealed that the synergy between PMB molecules and GO nanosheets greatly facilitated the vertical insertion of the nanocomposite into the lipid membrane, leading to membrane disturbance and permeabilization. Our results demonstrate a physical mechanism for improving the antibacterial performance of PMB and developing advanced antibacterial agents for better clinic uses.

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Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B

Zhang

Sun

et al. 2022

Polymers

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“…Depending on the type of tissue, cell membranes, the first biological interface for cellular interaction with LNPs, vary in compositions and properties. This is probably the reason that LNPs exhibit diverse binding abilities toward different tissues. ,− Indeed, the high efficacy of membrane-targeted agents (including proteins, peptides, and synthetic nanomedicines) against bacteria and tumor cells is attributed to their ability to distinguish between various types of cell membranes, based on intrinsic differences. − However, the mechanism underlying the membrane targeting of LNPs is still largely elusive.…”

Section: Introductionmentioning

confidence: 99%

Membrane-Specific Binding of 4 nm Lipid Nanoparticles Mediated by an Entropy-Driven Interaction Mechanism

Chen

Yuan

et al. 2022

ACS Nano

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Lipid nanoparticles (LNPs) are a leading biomimetic drug delivery platform due to their distinctive advantages and highly tunable formulations. A mechanistic understanding of the interaction between LNPs and cell membranes is essential for developing the cell-targeted carriers for precision medicine. Here the interactions between sub 10 nm cationic LNPs (cLNPs; e.g., 4 nm in size) and varying model cell membranes are systematically investigated using molecular dynamics simulations. We find that the membrane-binding behavior of cLNPs is governed by a two-step mechanism that is initiated by direct contact followed by a more crucial lipid exchange (dissociation of cLNP’s coating lipids and subsequent flip and intercalation into the membrane). Importantly, our simulations demonstrate that the membrane binding of cLNPs is an entropy-driven process, which thus enables cLNPs to differentiate between membranes having different lipid compositions (e.g., the outer and inner membranes of bacteria vs the red blood cell membranes). Accordingly, the possible strategies to drive the membrane-targeting behaviors of cLNPs, which mainly depend on the entropy change in the complicated entropy–enthalpy competition of the cLNP–membrane interaction process, are investigated. Our work unveils the molecular mechanism underlying the membrane selectivity of cLNPs and provides useful hints to develop cLNPs as membrane-targeting agents for precision medicine.

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Antibacterial Activity of Polymyxins Encapsulated in Nanocarriers Against Gram-Negative Bacteria

de Lacerda Coriolano,

de Souza,

Cavalcanti

et al. 2024

Indian J Microbiol

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Interactions between polymyxin B and various bacterial membrane mimics: A molecular dynamics study

Cited by 9 publications

References 59 publications

Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B

Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B

Membrane-Specific Binding of 4 nm Lipid Nanoparticles Mediated by an Entropy-Driven Interaction Mechanism

Antibacterial Activity of Polymyxins Encapsulated in Nanocarriers Against Gram-Negative Bacteria

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