Fujian Normal University, Fuzhou, Fujian, China.
PeerJ. 2022 Sep 14;10:e14010. doi: 10.7717/peerj.14010. eCollection 2022.
Antibiotic resistance of bacterial pathogens has become a severe threat to human health. To counteract antibiotic resistance, it is of significance to discover new antibiotics and also improve the efficacy of existing antibiotics. Here we show that 5-methylindole, a derivative of the interspecies signaling molecule indole, is able to directly kill various Gram-positive pathogens (., and ) and also Gram-negative ones (., and ), with 2-methylindole being less potent. Particularly, 5-methylindole can kill methicillin-resistant , multidrug-resistant , , and antibiotic-tolerant persisters. Furthermore, 5-methylindole significantly potentiates aminoglycoside antibiotics, but not fluoroquinolones, killing of . In addition, 5-iodoindole also potentiates aminoglycosides. Our findings open a new avenue to develop indole derivatives like 5-methylindole as antibacterial agents or adjuvants of aminoglycoside.
细菌病原体的抗生素耐药性已对人类健康构成严重威胁。为了对抗抗生素耐药性，发现新的抗生素并提高现有抗生素的疗效具有重要意义。在这里，我们发现 5-甲基吲哚，一种种间信号分子吲哚的衍生物，能够直接杀死各种革兰氏阳性病原体（如金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌）和革兰氏阴性病原体（如大肠杆菌、铜绿假单胞菌和鲍曼不动杆菌），而 2-甲基吲哚的作用较弱。特别地，5-甲基吲哚可以杀死耐甲氧西林的金黄色葡萄球菌、多药耐药菌、铜绿假单胞菌和抗生素耐受的枯草芽孢杆菌的持久期。此外，5-甲基吲哚显著增强了氨基糖苷类抗生素，但不是氟喹诺酮类药物对铜绿假单胞菌的杀伤作用。此外，5-碘吲哚也增强了氨基糖苷类药物的作用。我们的研究结果为开发 5-甲基吲哚等吲哚衍生物作为抗菌剂或氨基糖苷类抗生素的佐剂开辟了新途径。
