Sebak Mohamed, Mukku Venugopal, Saafan Amal E, Bakeer Walid, Abd-ELGhani Sameh, El-Gendy Ahmed O, Edrada-Ebel RuAngelie
Faculty of Science, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
Department of Pharmaceutical Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
Antonie Van Leeuwenhoek. 2025 May 10;118(6):77. doi: 10.1007/s10482-025-02087-8.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most alarming antibiotic-resistant pathogens causing nosocomial and community-acquired infections. Actinomycetes, particularly Streptomycetes, have historically been a major source of natural products including anti-MRSA agents. Hence, we designed this study to isolate new anti-MRSA natural products from Streptomycetes aided by liquid chromatography-electrospray ionization-high resolution mass spectrometry (LC-ESI-HRMS)-based metabolomics data analysis and dereplication study to select the best fractions for isolation work. Following this approach, two new natural products, namely, (4-propylphenyl) methane-diazonium (1) and (4E)-6-oxooctadec-4-enoic acid (2) and three known compounds, 8-methyl-5-oxononanoic acid (4), 15-methylhexadecanoic acid (5), and (Z)-14-methylpentadecenoic acid (6) were isolated from two soil Streptomyces sp. Additionally, (9E)-11-hydroxyoctadec-9-enoic acid (3) was recovered for the first time from Streptomycetes. The minimum inhibitory concentration (MIC) of compounds 1, 5, and 6 against MRSA were 128, 64, and 64 µg/mL respectively. The compounds were slightly more active against B. subtilis with MIC values of 64, 64, and 32 µg/mL, respectively. Our research adds to the growing knowledge about the importance of combining sophisticated analytical methods in the chemical profiling of the fractions with the outcomes of the bioassays throughout the subsequent fractionation processes to help isolate new secondary metabolites from natural sources.
耐甲氧西林金黄色葡萄球菌(MRSA)是引起医院感染和社区获得性感染的最令人担忧的抗生素耐药病原体之一。放线菌,特别是链霉菌,历来是包括抗MRSA药物在内的天然产物的主要来源。因此,我们设计了本研究,借助基于液相色谱 - 电喷雾电离 - 高分辨率质谱(LC-ESI-HRMS)的代谢组学数据分析和去重复研究,从链霉菌中分离新的抗MRSA天然产物,以选择最佳馏分进行分离工作。按照这种方法,从两种土壤链霉菌中分离出两种新的天然产物,即(4-丙基苯基)甲烷重氮盐(1)和(4E)-6-氧代十八碳-4-烯酸(2)以及三种已知化合物,8-甲基-5-氧代壬酸(4)、15-甲基十六烷酸(5)和(Z)-14-甲基十五碳烯酸(6)。此外,首次从链霉菌中回收了(9E)-11-羟基十八碳-9-烯酸(3)。化合物1、5和6对MRSA的最低抑菌浓度(MIC)分别为128、64和64μg/mL。这些化合物对枯草芽孢杆菌的活性略高,MIC值分别为64、64和32μg/mL。我们的研究增加了人们对在后续分馏过程中将复杂分析方法与生物测定结果相结合用于馏分化学分析以帮助从天然来源分离新的次生代谢物的重要性的认识。