School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.
Department of Life Sciences, Aberystwyth University, Wales, UK.
Probiotics Antimicrob Proteins. 2023 Feb;15(1):202-214. doi: 10.1007/s12602-022-10036-4. Epub 2022 Dec 31.
Antimicrobial resistance (AMR) is a global concern, and as soon as new antibiotics are introduced, resistance to those agents emerges. Therefore, there is an increased appetite for alternative antimicrobial agents to traditional antibiotics. Here, we used in silico methods to investigate potential antimicrobial peptides (AMPs) from predatory myxobacteria. Six hundred seventy-two potential AMP sequences were extracted from eight complete myxobacterial genomes. Most putative AMPs were predicted to be active against Klebsiella pneumoniae with least activity being predicted against Staphylococcus aureus. One hundred seventeen AMPs (defined here as 'potent putative AMPs') were predicted to have very good activity against more than two bacterial pathogens, and these were characterized further in silico. All potent putative AMPs were predicted to have anti-inflammatory and antifungal properties, but none was predicted to be active against viruses. Twenty six (22%) of them were predicted to be hemolytic to human erythrocytes, five were predicted to have anticancer properties, and 56 (47%) were predicted to be biofilm active. In vitro assays using four synthesized AMPs showed high MIC values (e.g. So_ce_56_913 250 µg/ml and Coral_AMP411 125 µg/ml against E. coli). However, antibiofilm assays showed a substantial reduction in numbers (e.g. Coral_AMP411 and Myxo_mac104 showed a 69% and 73% reduction, respectively, at the lowest concentration against E. coli) compared to traditional antibiotics. Fourteen putative AMPs had high sequence similarity to proteins which were functionally associated with proteins of known function. The myxobacterial genomes also possessed a variety of biosynthetic gene clusters (BGCs) that can encode antimicrobial secondary metabolites, but their numbers did not correlate with those of the AMPs. We suggest that AMPs from myxobacteria are a promising source of novel antimicrobial agents with a plethora of biological properties.
抗微生物药物耐药性（AMR）是一个全球性的问题，只要新的抗生素被引入，这些药物的耐药性就会出现。因此，人们对传统抗生素的替代抗菌药物的需求不断增加。在这里，我们使用计算机模拟方法来研究捕食性粘细菌的潜在抗菌肽（AMPs）。从八个完整的粘细菌基因组中提取了 672 个潜在的 AMP 序列。大多数推定的 AMP 被预测对肺炎克雷伯菌具有活性，对金黄色葡萄球菌的活性最低。117 种 AMP（此处定义为“有效推定 AMP”）被预测对超过两种细菌病原体具有很好的活性，并且这些 AMP 在计算机上进一步进行了特征描述。所有有效的推定 AMP 都被预测具有抗炎和抗真菌特性，但没有一种被预测对病毒具有活性。其中 26 种（22%）被预测对人红细胞具有溶血作用，5 种被预测具有抗癌特性，56 种（47%）被预测具有生物膜活性。使用四种合成 AMP 进行的体外试验显示 MIC 值较高（例如，So_ce_56_913 对大肠杆菌的 MIC 值为 250µg/ml，Coral_AMP411 为 125µg/ml）。然而，抗生物膜试验显示数量有显著减少（例如，Coral_AMP411 和 Myxo_mac104 对大肠杆菌的最低浓度分别减少了 69%和 73%），与传统抗生素相比。有 14 种推定的 AMP 与具有已知功能的蛋白质的功能相关的蛋白质具有很高的序列相似性。粘细菌基因组还拥有各种可以编码抗菌次级代谢物的生物合成基因簇（BGCs），但它们的数量与 AMPs 没有相关性。我们认为，粘细菌的 AMP 是一种很有前途的新型抗菌药物来源，具有多种生物学特性。
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