Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium.
Microb Biotechnol. 2022 Dec;15(12):2917-2928. doi: 10.1111/1751-7915.14160. Epub 2022 Nov 5.
Indole signalling has been proposed as a potential target for the development of novel virulence inhibitors to control bacterial infections. However, the major structural features of indole analogues that govern antivirulence activity remain unexplored. Therefore, we investigated the impact of 26 indole analogues on indole-regulated virulence phenotypes in Vibrio campbellii and on the virulence of the bacterium in a gnotobiotic brine shrimp model. The results demonstrated that 10 indole analogues significantly increased the fluorescence of indole reporter strain Vibrio cholerae S9149, 21 of them decreased the swimming motility of V. campbellii, and 13 of them significantly decreased the biofilm formation of V. campbellii. Further, we found that 1-methylindole, indene, 2,3-benzofuran, thianaphthene, indole-3-acetonitrile, methyl indole-3-carboxylate, 3-methylindole, and indole-2-carboxaldehyde exhibited a significant protective effect on brine shrimp larvae against V. campbellii infection, resulting in survival rates of challenged brine shrimp above 80%. The highest survival of shrimp larvae (98%) was obtained with indole-3-acetonitrile, even at a relatively low concentration of 20 μM. Importantly, the indole analogues did not affect bacterial growth, both in vitro and in vivo. These results indicate the potential of indole analogues in applications aiming at the protection of shrimp from vibriosis.
吲哚信号已被提议作为开发新型毒力抑制剂以控制细菌感染的潜在目标。然而，控制抗病毒活性的吲哚类似物的主要结构特征仍未得到探索。因此，我们研究了 26 种吲哚类似物对弧菌属 Campbellii 中吲哚调节的毒力表型以及它们在无菌丰年虾模型中对细菌毒力的影响。结果表明，10 种吲哚类似物显著增加了吲哚报告菌株霍乱弧菌 S9149 的荧光，其中 21 种降低了弧菌属 Campbellii 的游动能力，13 种显著降低了弧菌属 Campbellii 的生物膜形成。此外，我们发现 1-甲基吲哚、茚、2,3-苯并呋喃、噻吩、吲哚-3-乙腈、甲基吲哚-3-羧酸酯、3-甲基吲哚和吲哚-2-甲醛对丰年虾幼虫抵御弧菌属 Campbellii 感染具有显著的保护作用，导致受挑战的丰年虾幼虫的存活率超过 80%。用吲哚-3-乙腈甚至在相对较低的 20 μM 浓度下，虾幼虫的存活率最高（98%）。重要的是，吲哚类似物在体外和体内均不影响细菌生长。这些结果表明吲哚类似物在保护虾类免受弧菌病方面具有应用潜力。
