Pressure-driven membrane inflation through nanopores on the cell wall

Zhong, Qi; Wu, Chen–Xu; Ma, Rui

doi:10.1088/1674-1056/acd7cc

Cited by 3 publications

(3 citation statements)

References 66 publications

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“…While the cell wall is the initial porous barrier that permits the movement of substances between the cell and its environment, it allows antimicrobial peptides to enter the periplasmic space or area just outside the cell membrane in certain organisms [ 46 ]. However, the cell membrane acts as the main barrier, preventing these peptides from entering the cell’s interior.…”

Section: Resultsmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens’ quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae’s chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP’s stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

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Section: Resultsmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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show abstract

“…This suggests that DP1 and DP2 facilitate higher charge transmission, forming stable interactions with the target protein, thereby enhancing bioactivity compared to NoPv1, as displayed in Table 5 and Figure 8. While the cell wall aids substance movement between the cell and its surroundings, it also allows antimicrobial peptides to enter the periplasmic space, or the region adjacent to the cell membrane, in specific organisms [23]. Although the cell membrane acts as the…”

Section: Frontier Molecular Orbitals Analysismentioning

confidence: 99%

“…While the cell wall aids substance movement between the cell and its surroundings, it also allows antimicrobial peptides to enter the periplasmic space, or the region adjacent to the cell membrane, in specific organisms [23]. Although the cell membrane acts as the primary barrier against peptide entry into the cell interior, it must overcome its defenses to access intracellular targets and carry out antimicrobial functions.…”

Section: Transmembrane Mechanism Of Dp1 and Dp2mentioning

confidence: 99%

Mechanism Analysis of Antimicrobial Peptide NoPv1 Related to Potato Late Blight through a Computer-Aided Study

Zhou,

Wen,

2024

IJMS

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Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight.

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Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

Zhang 张,

Xu 徐,

Ma 马

et al. 2024

Chinese Phys. B

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Membrane tension plays a crucial role in various fundamental cellular processes, with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force. However, the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive. In this study, we investigated the correlation between membrane tension and poration activity of melittin, a prototypical pore-forming peptide, using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis, molecular dynamics simulations, and live cell assays. The results demonstrate that an increase in membrane tension enhances the activity of melittin, particularly near its critical pore-forming concentration. Moreover, peptide actions such as binding, insertion, and aggregation in the membrane further influence the evolution of membrane tension. Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin's ability to induce pore formation and disrupt membranes, resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0 μg mL-1 melittin. Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin, while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.

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Pressure-driven membrane inflation through nanopores on the cell wall

Cited by 3 publications

References 66 publications

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Mechanism Analysis of Antimicrobial Peptide NoPv1 Related to Potato Late Blight through a Computer-Aided Study

Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

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