Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India.
Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Free Radic Biol Med. 2018 May 20;120:62-71. doi: 10.1016/j.freeradbiomed.2018.03.021. Epub 2018 Mar 15.
Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly. Hydroxychavicol (HC) isolated from Piper betle has been reported to possess antibacterial activity. It is currently not clear how the antibacterial activity of HC is manifested. In this investigation we show HC generates superoxide in E. coli cells. Antioxidants protected E. coli against HC induced cell death while gshA mutant was more sensitive to HC than wild type. DNA damage repair deficient mutants are hypersensitive to HC and HC induces the expression of DNA damage repair genes that repair oxidative DNA damage. HC treated E. coli cells are inhibited from growth and undergo DNA condensation. In vitro HC binds to DNA and cleaves it in presence of copper. Our data strongly indicates HC mediates bacterial cell death by ROS generation and DNA damage. Damage to iron sulfur proteins in the cells contribute to amplification of oxidative stress initiated by HC. Further HC is active against a number of Gram negative bacteria isolated from patients with a wide range of clinical symptoms and varied antibiotic resistance profiles.
抗生素耐药性是一个全球性问题，迫切需要增强对抗致病细菌的武器库。不同耐药细菌的出现威胁着人类生命，使人类有可能回到抗生素前时代。植物来源仍然是具有抗菌特性的各种有机分子的重要来源，并且可以增强现有的抗菌分子。胡椒，一种攀援植物，广泛分布于南亚和东南亚，其叶子和坚果经常被食用。从胡椒中分离出的胡椒基甲醚已被报道具有抗菌活性。目前尚不清楚 HC 的抗菌活性是如何表现的。在这项研究中，我们表明 HC 在大肠杆菌细胞中产生超氧化物。抗氧化剂可保护大肠杆菌免受 HC 诱导的细胞死亡，而 gshA 突变体比野生型对 HC 更敏感。缺乏 DNA 损伤修复能力的突变体对 HC 更为敏感，HC 诱导修复氧化 DNA 损伤的 DNA 损伤修复基因的表达。HC 处理的大肠杆菌细胞生长受到抑制并发生 DNA 凝聚。体外实验中，HC 在铜存在的情况下与 DNA 结合并将其切割。我们的数据强烈表明，HC 通过 ROS 生成和 DNA 损伤介导细菌细胞死亡。细胞中铁硫蛋白的损伤导致 HC 引发的氧化应激放大。此外，HC 对从具有广泛临床症状和不同抗生素耐药谱的患者中分离出的多种革兰氏阴性菌具有活性。
