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疏水分子对生物膜的破坏:一种抑制细菌生长的方法。

Disruption of biological membranes by hydrophobic molecules: a way to inhibit bacterial growth.

作者信息

Valdez-Lara Alejandra Gabriela, Jaramillo-Granada Ángela M, Ortega-Zambrano Daniel, García-Marquez Eristeo, García-Fajardo Jorge Alberto, Mercado-Uribe H, Ruiz-Suárez J C

机构信息

Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Unidad Monterrey, Apodaca, Nuevo León, Mexico.

Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco Subsede Noreste, Apodaca, Nuevo León, Mexico.

出版信息

Front Microbiol. 2025 Jan 8;15:1478519. doi: 10.3389/fmicb.2024.1478519. eCollection 2024.

DOI:10.3389/fmicb.2024.1478519
PMID:39845054
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11750777/
Abstract

With antibiotic resistance increasing in the global population every year, efforts to discover new strategies against microbial diseases are urgently needed. One of the new therapeutic targets is the bacterial cell membrane since, in the event of a drastic alteration, it can cause cell death. We propose the utilization of hydrophobic molecules, namely, propofol (PFL) and cannabidiol (CBD), dissolved in nanodroplets of oil, to effectively strike the membrane of two well-known pathogens: and . First, we carried out calorimetric measurements to evaluate the effects of these drugs on model membranes formed by lipids from these bacteria. We found that the drugs modify their transition temperature, enthalpy of cohesion, and cooperativity, which indicates a strong alteration of the membranes. Then, inhibition of colony-forming units is studied in incubation experiments. Finally, we demonstrate, using atomic force and fluorescence microscopy, that the drugs, especially propofol, produce a visible disruption in real bacterial membranes, explaining the observed inhibition. These findings may have useful implications in the global effort to discover new ways to effectively combat the growing threat of drug-resistant pathogens, especially in skin infections.

摘要

随着全球人群中抗生素耐药性逐年增加,迫切需要努力探索对抗微生物疾病的新策略。新的治疗靶点之一是细菌细胞膜,因为一旦发生剧烈改变,它会导致细胞死亡。我们提议利用溶解在油纳米液滴中的疏水分子,即丙泊酚(PFL)和大麻二酚(CBD),来有效攻击两种著名病原体的膜: 和 。首先,我们进行了量热测量,以评估这些药物对由这些细菌的脂质形成的模型膜的影响。我们发现这些药物改变了它们的转变温度、内聚焓和协同性,这表明膜发生了强烈改变。然后,在孵育实验中研究了集落形成单位的抑制情况。最后,我们使用原子力显微镜和荧光显微镜证明,这些药物,尤其是丙泊酚,会在真实细菌膜上产生明显破坏,这解释了观察到的抑制现象。这些发现可能对全球努力发现有效对抗耐药病原体日益增长威胁的新方法具有有益影响,尤其是在皮肤感染方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/a28ace1d57f5/fmicb-15-1478519-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/54d77a6293f3/fmicb-15-1478519-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/e80e05e3a4e6/fmicb-15-1478519-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/fa6da68d7005/fmicb-15-1478519-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/691f9d339253/fmicb-15-1478519-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/8e80312e454e/fmicb-15-1478519-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/a28ace1d57f5/fmicb-15-1478519-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/54d77a6293f3/fmicb-15-1478519-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/e80e05e3a4e6/fmicb-15-1478519-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/fa6da68d7005/fmicb-15-1478519-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/691f9d339253/fmicb-15-1478519-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/8e80312e454e/fmicb-15-1478519-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a2/11750777/a28ace1d57f5/fmicb-15-1478519-g0006.jpg

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本文引用的文献

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Development of nanoemulsions for the delivery of hydrophobic and hydrophilic compounds against carbapenem-resistant .用于递送疏水性和亲水性化合物以对抗耐碳青霉烯类药物的纳米乳剂的研发
RSC Adv. 2022 Sep 16;12(40):26455-26462. doi: 10.1039/d2ra03925g. eCollection 2022 Sep 12.
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Erythro-PmBs: A Selective Polymyxin B Delivery System Using Antibody-Conjugated Hybrid Erythrocyte Liposomes.红细胞-PmBs:一种使用抗体偶联杂交红细胞脂质体的选择性多粘菌素 B 递药系统。
ACS Infect Dis. 2022 Oct 14;8(10):2059-2072. doi: 10.1021/acsinfecdis.2c00017. Epub 2022 Sep 29.
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Out of control: The need for standardised solvent approaches and data reporting in antibiofilm assays incorporating dimethyl-sulfoxide (DMSO).
失控:在包含二甲基亚砜(DMSO)的抗生物膜测定中,对标准化溶剂方法和数据报告的需求。
Biofilm. 2022 Aug 17;4:100081. doi: 10.1016/j.bioflm.2022.100081. eCollection 2022 Dec.
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Differential Interaction of Cannabidiol with Biomembranes Dependent on Cholesterol Concentration.大麻二酚与生物膜的差异相互作用取决于胆固醇浓度。
ACS Chem Neurosci. 2022 Apr 6;13(7):1046-1054. doi: 10.1021/acschemneuro.2c00040. Epub 2022 Mar 17.
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Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.2019 年全球细菌对抗菌药物耐药性的负担:系统分析。
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