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Replication Data for: \"Lulworthinone: In vitro mode of action investigation of an antibacterial dimeric naphthopyrone isolated from a marine fungus.\"

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DataONE2022-03-15 更新2024-06-08 收录
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Treatment options for infections caused by antimicrobial-resistant bacteria are rendered ineffective, and drug alternatives are needed - either from new chemical classes or drugs with new modes of action. Historically, natural products have been important contributors to drug discovery. The search for new antimicrobials from marine fungi led to the discovery of the dimeric naphthopyrone lulworthinone produced by an obligate marine fungus in the family Lulworthiaceae (Jenssen et al. ,2021). The observed potent antibacterial activity against Gram positive bacteria, including several clinical methicillin-resistant _Staphylococcus aureus_ (MRSA) isolates, promoted this follow-up mode of action investigation. Lulworthinone treatment induced an upregulation of genes responding to cell envelope stress in Bacillus subtilis. Further in vitro assays, focusing on membrane integrity and membrane potential, indicated that the compound is active on the bacterial membrane without destroying it. This was supported by NMR experiments using artificial lipid bilayers. Fluorescence microscopy revealed that lulworthinone affects cell morphology and interferes with the localization of the cell division protein FtsZ which might lead to impaired cell division. Surface plasmon resonance spectrometry and dynamic light scattering assays showed that this activity is linked with the compound's ability to form colloidal aggregates. Antibacterial agents targeting the bacterial membrane are of special interest since resistance development against such compounds seems harder to achieve and sustain. This dataset is consists of six zip files containing the results from in vivo assays focused on biosensors, membrane integrity, membrane potential, Time-kill curves; pharmacodynamic modelling and microscopy pictures.

由抗微生物耐药菌(antimicrobial-resistant bacteria)引发的感染,其现有治疗方案已失去效用,亟需来自全新化学骨架或具备全新作用机制的替代药物。长期以来,天然产物始终是药物发现领域的重要源泉。科研人员从海洋真菌中筛选新型抗菌剂时,发现了由卢沃斯氏菌科(Lulworthiaceae)专性海洋真菌产生的二聚萘并吡喃酮类化合物卢氏菌素(lulworthinone)(Jenssen等人,2021)。该化合物对革兰氏阳性菌展现出强效抗菌活性,涵盖多株临床分离的耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA),这一发现推动了后续的作用机制研究。实验表明,卢氏菌素处理可诱导枯草芽孢杆菌(Bacillus subtilis)中应对细胞包膜应激的基因表达上调。后续以膜完整性与膜电位为核心的体外实验显示,该化合物可作用于细菌细胞膜但不会破坏其结构,该结论得到了人工脂质双层核磁共振(nuclear magnetic resonance,NMR)实验的佐证。荧光显微镜观测结果显示,卢氏菌素会影响细菌细胞形态,并干扰细胞分裂蛋白FtsZ的定位,进而可能导致细胞分裂功能受损。表面等离子体共振光谱法(surface plasmon resonance spectrometry,SPR)与动态光散射(dynamic light scattering,DLS)实验证实,该抗菌活性与化合物形成胶体聚集体的能力密切相关。靶向细菌细胞膜的抗菌剂备受关注,因为针对此类化合物的耐药性似乎更难产生且难以维持。本数据集包含6个压缩文件包,涵盖了针对生物传感器、膜完整性、膜电位、时间杀菌曲线、药效学建模以及显微镜图像的体内实验结果。

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2024-01-05
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