Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane-Antibiotic Interactions.
Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane-Antibiotic Interactions.
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DOI：
10.3390/bios14010045
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发表时间：
2024-01-15
期刊：
影响因子：
5.4
通讯作者：
Daniel, Susan
中科院分区：
文献类型：
--
作者：
Bint-E-Naser, Samavi Farnush;Mohamed, Zeinab Jushkun;Chao, Zhongmou;Bali, Karan;Owens, Roisin M.;Daniel, Susan
关键词：
随着膜介导的抗生素耐药性在革兰氏阳性菌中不断发展，开发新的方法来阐明涉及抗生素耐药性的膜特性已变得至关重要。革兰氏阳性菌胞质膜分泌的膜囊泡（MVs）含有天然成分，保存脂质和蛋白质多样性，核酸，有时还有毒力因子。因此，mv衍生的膜平台为革兰氏阳性细菌膜提供了一个很好的模型。在这项工作中，我们报道了一种基于平面细菌细胞质膜的生物传感器的开发，该生物传感器使用从枯草芽孢杆菌WT菌株中分离出来的mv，可以涂覆在多种表面类型上，如玻璃、石英晶体和聚合物电极，促进药物膜相互作用的多模态评估。保留天然膜成分，如脂质胆酸，脂质和蛋白质被证实。该生物传感器复制了抗菌化合物达托霉素与革兰氏阳性细菌膜的已知相互作用模式，建立了该平台的适用性，用于进行膜作用抗生素化合物与细菌细胞质膜相互作用的生物物理表征。我们报告了当钙离子存在于达托霉素时，而不存在钙离子时，膜粘弹性和通透性的变化对应于部分膜破坏。这种基于生物膜的生物传感平台能够评估暴露于抗生素候选药物期间的膜生物物理特性，以帮助识别以膜破坏为目标的化合物作为作用机制。
As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug–membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are absent. This biomembrane-based biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.
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影响因子：
4.9
作者：
ALBORN, WE;ALLEN, NE;PRESTON, DA
通讯作者：
PRESTON, DA
影响因子：
4.9
作者：
Hachmann, Anna-Barbara;Sevim, Elif;Helmann, John D.
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Helmann, John D.
影响因子：
5.2
作者：
Hobbs, Joanne Karen;Miller, Keith;Chopra, Ian
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Chopra, Ian
影响因子：
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作者：
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通讯作者：
Alabi, Christopher A.
影响因子：
3.2
作者：
Chwastek, Grzegorz;Petrov, Eugene P.;Saenz, James Peter
通讯作者：
Saenz, James Peter