INSERM, Univ. Rennes, INRA, CHU Rennes, Nutrition Metabolisms and Cancer (NuMeCan), UMR-1241, Biosit, MRic/ISFR, Rennes, France; Laboratory of Microbiology, Department of Life and Earth Sciences, Faculty of Sciences I, Lebanese University, Hadath Campus, Beirut, Lebanon.
INSERM, Univ. Rennes, INRA, CHU Rennes, Nutrition Metabolisms and Cancer (NuMeCan), UMR-1241, Biosit, MRic/ISFR, Rennes, France.
Fitoterapia. 2019 Sep;137:104274. doi: 10.1016/j.fitote.2019.104274. Epub 2019 Jul 22.
We have previously demonstrated that out of the butyrolactones series synthesized based on the natural lichen metabolite lichesterinic acid, compound (B-13) was the most effective against oral bacteria. However, its antibacterial mechanism is still unknown. In this study, we have investigated its bacterial localization by synthesizing a fluorescently labeled B-13 with NBD while maintaining its antibacterial activity. We showed that this compound binds to Streptococcus gordonii cell surface, as demonstrated by HPLC analysis. By adhering to cell surface, B-13 induced cell wall disruption leading to the release of bacterial constituents and consequently, the death of S. gordonii, a Gram-positive bacterium. A Gram-negative counterpart, Porphyromanas gingivalis, showed also cracked and ruptured cells in the presence of B-13. Besides, we also demonstrated that the analog of B-13, B-12, has also induced disruption of P. gingivalis and S. gordonii. This study revealed that butyrolactones can be considered as potent antibacterial compounds against oral pathogens causing medical complications.
我们之前已经证明，在所合成的基于天然地衣代谢产物lichensterinic 酸的丁内酯系列化合物中，化合物 (B-13) 对口腔细菌最有效。然而，其抗菌机制尚不清楚。在这项研究中，我们通过用 NBD 标记荧光 B-13 合成来研究其细菌定位，同时保持其抗菌活性。我们表明，该化合物与链球菌结合，如 HPLC 分析所示。通过粘附在细胞表面，B-13 诱导细胞壁破裂，导致细菌成分的释放，从而导致革兰氏阳性菌 S. gordonii 的死亡。革兰氏阴性对照物牙龈卟啉单胞菌在存在 B-13 的情况下也显示出破裂和破裂的细胞。此外，我们还证明了 B-13 的类似物 B-12 也诱导了牙龈卟啉单胞菌和 S. gordonii 的破坏。这项研究表明，丁内酯可以被认为是一种对抗引起医疗并发症的口腔病原体的有效抗菌化合物。
