Ben Selma Walid, Farouk Amr, Ban Zhaojun, Ferjeni Mohamed, Alsulami Tawfiq, Ali Hatem, Boukadida Jalel
Laboratory of Biological and Genetic Markers Studying for Early Diagnosis and Follow-up of Neurological Diseases, Faculty of Medicine - Av. Ibn el Jazzar-4000, Sousse, LR18ES47, Tunisia.
Higher Institute of Applied Sciences and Technology, Mahdia, Tunisia.
Heliyon. 2024 Sep 24;10(19):e38281. doi: 10.1016/j.heliyon.2024.e38281. eCollection 2024 Oct 15.
Due to the increasing resistance prevalence to the last line of antibiotics, such as colistin, and the rising threat of multi-drug resistant bacteria, it is crucial to find alternative therapeutic options. The current study focuses on evaluating antibacterial activities alone and in combination with colistin of essential oil (TA-EO) against colistin-resistant , , and co-harboring -1 gene. GC/MS was used to determine the chemical composition of TA-EO. Disc diffusion and microdilution techniques were used to evaluate the antimicrobial activities of TA-EO. Synergism between colistin and TA-EO was evaluated by checkerboard assay. The major compounds of TA-EO were docked with known enzymes involved in resistance to colistin, as well as the biosynthesis of peptidoglycan and amino acids. GC/MS revealed that TA-EO was of carvacrol chemotype (67.94 %). The TA-EO showed remarkable antibacterial activities against all Gram-negative bacterial strains, with the diameter of inhibition zones varied between 30 and 50 mm and a ratio MBC/MIC equal to 1 for the vast majority of bacterial isolates. Interestingly, the checkerboard showed synergism between TA-EO and colistin against colistin-resistant co-harboring -1 gene (FICI˂1) and reduced the MIC of colistin by 16- to 512-fold and those of TA-EO by 4- to 16-fold. The docking study demonstrated that carvacrol had high binding free energies against MCR-1, a phosphoethanolamine transferase extracellular domain, and its catalytic domain implicated in resistance to colistin, and undecaprenyl pyrophosphate synthase in complex with magnesium which is involved in bacterial peptidoglycan biosynthesis. The molecular dynamics study for 100-ns also revealed the stability of the MCR-1/carvacrol complex with a constant surface area over the simulation. These results support using carvacrol or TA-EO as a bactericidal agent, either alone or in combination with colistin, to treat infections caused by colistin-resistant Gram-negative bacteria.
由于对诸如黏菌素等最后一线抗生素的耐药性日益普遍，以及多重耐药细菌构成的威胁不断增加，寻找替代治疗方案至关重要。当前的研究聚焦于评估香芹酚精油（TA-EO）单独以及与黏菌素联合针对携带mcr-1基因的耐黏菌素肺炎克雷伯菌、大肠埃希菌和鲍曼不动杆菌的抗菌活性。采用气相色谱/质谱联用（GC/MS）来确定TA-EO的化学成分。采用纸片扩散法和微量稀释技术评估TA-EO的抗菌活性。通过棋盘法评估黏菌素与TA-EO之间的协同作用。将TA-EO的主要化合物与已知的参与黏菌素耐药性以及肽聚糖和氨基酸生物合成的酶进行对接。GC/MS显示TA-EO为香芹酚化学型（67.94%）。TA-EO对所有革兰氏阴性菌菌株均表现出显著的抗菌活性，抑菌圈直径在30至50毫米之间，并且绝大多数细菌分离株的最低杀菌浓度（MBC）与最低抑菌浓度（MIC）之比等于1。有趣的是，棋盘法显示TA-EO与黏菌素对携带mcr-1基因的耐黏菌素鲍曼不动杆菌具有协同作用（分数抑菌浓度指数FICI˂1），并将黏菌素的MIC降低了16至512倍，将TA-EO的MIC降低了4至16倍。对接研究表明，香芹酚对MCR-1（一种磷酸乙醇胺转移酶胞外结构域）及其与黏菌素耐药性相关的催化结构域以及与参与细菌肽聚糖生物合成的镁结合的十一异戊烯焦磷酸合酶具有高结合自由能。100纳秒的分子动力学研究还揭示了在模拟过程中MCR-1/香芹酚复合物具有恒定表面积的稳定性。这些结果支持将香芹酚或TA-EO单独或与黏菌素联合用作杀菌剂，以治疗由耐黏菌素革兰氏阴性菌引起的感染。
