Centre for Biotechnology, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India.
Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Arch Microbiol. 2024 Nov 2;206(12):453. doi: 10.1007/s00203-024-04189-9.
Tuberculosis (TB) continues to be a primary worldwide health concern due to relatively ineffective treatments. The prolonged duration of conventional antibiotic therapy warrants innovative approaches to shorten treatment courses. In response to challenges, the study explores potential of Ajoene, a naturally occurring garlic extract-derived compound, for potential TB treatment. Mycobacterium smegmatis as a model organism for M. tuberculosis (M. tb) to investigate Ajoene's efficiency. In vitro techniques like antimicrobial susceptibility, antibiofilm, EtBr accumulation assay, and ROS assay evaluate the potency of Ajoene and conventional TB drugs against Mycobacterium smegmatis. An in-silico study also investigated the interaction between Ajoene and quorum-sensing proteins, specifically regX3, MSMEG_5244, and MSMEG_3944, which are involved in biofilm formation and sliding activity. In vitro findings revealed that Ajoene exhibited significant antibacterial activity by inhibiting growth and showing bactericidal effects. It also demonstrated additive interactions with common antibiotics such as Isoniazid and Rifampicin. Furthermore, Ajoene demonstrated a comparative interaction with commonly used antibiotics, such as Isoniazid and Rifampicin, and reduced M. smegmatis motility, both alone and in combination with these antibiotics. In silico analysis shows that Ajoene exhibited a higher binding affinity with regX3, a protein orthologous to the regX3 gene in M.tb. Ajoene also demonstrated consistent antibiofilm effects, particularly when combined synergistically with Isoniazid and Rifampicin. Mechanistic investigations demonstrated Ajoene's potential to inhibit efflux pumps and promote ROS generation in bacteria, suggesting a potential direct killing mechanism. Collectively, the findings emphasize Ajoene's effectiveness as a novel antimycobacterial and antibiofilm molecule for TB treatment.
结核病（TB）仍然是全球主要的健康关注点，因为现有的治疗方法相对不够有效。传统抗生素治疗的疗程较长，这就需要创新的方法来缩短治疗过程。针对这一挑战，本研究探索了天然大蒜提取物衍生化合物 ajoene 治疗结核病的潜力。我们选择了 Mycobacterium smegmatis 作为 M. tuberculosis（M. tb）的模型生物，以研究 ajoene 的功效。体外技术，如抗菌药敏试验、抗生物膜、EtBr 积累试验和 ROS 试验，评估了 ajoene 和传统结核病药物对 Mycobacterium smegmatis 的效力。一项计算机模拟研究还研究了 ajoene 与群体感应蛋白（特别是参与生物膜形成和滑动活动的 regX3、MSMEG_5244 和 MSMEG_3944）之间的相互作用。体外研究结果表明 ajoene 通过抑制生长和表现出杀菌作用显示出显著的抗菌活性。它还与常用抗生素如异烟肼和利福平表现出相加相互作用。此外，ajoene 单独或与这些抗生素联合使用时，均能降低 M. smegmatis 的运动性，并与常用抗生素如异烟肼和利福平具有相似的相互作用。计算机模拟分析表明 ajoene 与 regX3 具有更高的结合亲和力，regX3 是 M.tb 中 regX3 基因的同源蛋白。Ajoene 还表现出一致的抗生物膜作用，特别是与异烟肼和利福平协同作用时。机制研究表明 ajoene 具有抑制外排泵和促进细菌中 ROS 产生的潜力，提示其具有潜在的直接杀菌机制。总的来说，这些发现强调了 ajoene 作为一种新型抗分枝杆菌和抗生物膜分子在结核病治疗中的有效性。
