Research Institute for Medical and Health sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Research Institute for Medical and Health sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; Department of Clinical Sciences, College of Medicine, University of Sharjah, P.O. Box 27272, United Arab Emirates.
Chem Biol Interact. 2021 Jan 5;333:109318. doi: 10.1016/j.cbi.2020.109318. Epub 2020 Nov 10.
Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.
由于威胁到控制常见传染病的能力，导致疾病延长、残疾和死亡，全球范围内的抗菌药物耐药性风险日益增加。在这方面，我们受到植物中有效化学生理机制的启发，这些机制是为了克服微生物的发病机制和进化的耐药性而进化的。肉桂醛以前被报道为沙拐枣精油中的主要抗菌成分。肉桂醛的毒性限制了其在人类医学中的应用。另一方面，与肉桂醛相比，植物总提取物表现出相似的抗菌活性，同时保持较低的毒性，尽管它含有肉桂醛的 22 倍。因此，我们假设植物提取物中的其他成分专门影响细菌而不影响哺乳动物细胞。我们采用了基于生物测定的分级分离方法，并结合不同植物提取物的比较代谢组学分析。结果揭示了存在细菌种特异性植物化学物质。肉桂酰亚油酸和亚油酸增强了肉桂醛和氨苄西林对金黄色葡萄球菌（包括耐甲氧西林金黄色葡萄球菌）的抗菌活性，而癸醛和肉桂酰亚油酸增强了对大肠杆菌的活性。计算建模和酶抑制试验表明，肉桂酰亚油酸选择性地与细菌核糖体 RNA 甲基转移酶结合，这是一种参与多药耐药细菌毒力和耐药性的重要酶。获得的结果可用于未来制备含有肉桂酰亚油酸的药物配方，以克服微生物进化的多药耐药行为。
