The rapid emergence of resistance in pathogenic bacteria together with a steep decline in economic incentives has rendered a new wave in the drug development by the pharmaceutical industry and researchers. Since cyanobacteria are recognized as wide producers of pharmaceutically important compounds, we investigated thirty-four cyanobacterial extracts prepared by solvents of different polarities for their antimicrobial potential. Almost all tested cyanobacterial strains exhibited some degree of antimicrobial bioactivity, with more general effect on fungal strains compared with bacteria. Surprisingly ~50% of cyanobacterial extracts exhibited specific activity against one or few bacterial indicator strains with Gram-positive bacteria being more affected. Extracts of two most promising strains were subjected to activity-guided fractionation and determination of the minimum inhibitory concentration (MIC) against selected bacterial and fungal isolates. Multiple fractions were responsible for their antimicrobial effect with MIC reaching low-micromolar concentrations and in some of them high level of specificity was recorded. Twenty-six bioactive fractions analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) online workflow using dereplication resulted in identification of only forty-nine peptide spectrum matches (PSMs) with eleven unique metabolites spectrum matches (MSMs). Interestingly, only three fractions from Nostoc calcicola Lukešová 3/97 and four fractions from Desmonostoc sp. Cc2 showed the presence of unique MSMs suggesting the presence of unknown antimicrobial metabolites among majority of bioactive fractions from both the strains. Our results highlight potential for isolation and discovery of potential antimicrobial bioactive lead molecules from cyanobacterial extracts.

中文翻译：

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使用基于MS / MS的分子网络技术对胞质蓝细菌菌株进行抗菌活性和生物活性分析。

致病菌耐药性的迅速出现以及经济诱因的急剧下降，在制药行业和研究人员的药物开发中掀起了新的浪潮。由于蓝细菌是公认的重要药物的广泛生产者，因此我们研究了34种由不同极性溶剂制备的蓝细菌提取物的抗菌潜力。几乎所有测试的蓝细菌菌株均表现出一定程度的抗菌生物活性，与细菌相比，其对真菌菌株的影响更大。令人惊讶的是，约50％的蓝细菌提取物表现出针对一种或几种细菌指示剂菌株的比活性，而革兰氏阳性细菌受到的影响更大。对两种最有希望的菌株的提取物进行活性引导分离，并确定对所选细菌和真菌分离株的最小抑制浓度（MIC）。MIC达到低微摩尔浓度时，多个组分负责其抗微生物作用，并在其中一些中记录了高特异性。使用去重复在LC-HRMS / MS和全球天然产物社会分子网络（GNPS）在线工作流程上分析了26种生物活性馏分，仅鉴定出49种肽谱匹配（PSM）和11种独特的代谢物谱匹配（MSM）。有趣的是，仅来自Nostoc calcicolaLukešová3/97的三个馏分和来自Desmonostoc sp。的四个馏分。Cc2显示了独特的MSM的存在，表明这两种菌株的大多数生物活性组分中都存在未知的抗微生物代谢产物。我们的结果突出了从蓝细菌提取物中分离和发现潜在抗菌生物活性铅分子的潜力。