二甲双胍（MeT）是一种经FDA批准的药物，具有众多的健康益处。除了作为一种抗糖尿病药物外，MeT对各种癌症、肝脏疾病、心血管疾病和肾脏疾病也具有疗效。本研究旨在检验其作为抗机会性细菌病原体假单胞菌的抗毒力药物的独特潜力。由于致病微生物多重耐药的威胁，许多具有抗毒力前景的新型或重新使用的药物正在作为下一代治疗方法涌现，旨在超越现有抗微生物治疗方案的应用。假单胞菌的群体感应（QS）机制是抑制细菌毒性的一种有吸引力的药物靶点。在这种背景下，使用生物传感器分析了MeT的抗QS潜力。在体外系统中，MeT全面评估了对假单胞菌不同游动表型的影响、细菌毒力因子的生产（表型和基因型表达）以及生物膜发育。在亚致死浓度下，MeT具有丰富的群体感应熄灭（QQ）能力，并显著抑制了假单胞菌中的Acylated homoserine lactone(AHL)生物合成。此外，MeT（1/8最小抑菌浓度）有效下调了假單胞菌中各种QS和毒力基因的表达水平，这与藻酸盐、溶血素、青绿假单胞菌素、青绿素、弹性蛋白酶和蛋白酶的生产水平明显降低相一致。分子对接的体外分析还预测到MeT与假单胞菌的QS受体之间有着强烈的相互作用。MeT还破坏了细菌的游动表型，并通过抑制EPS的产生成功地废除了假单胞菌的生物膜形成。因此，在临床环境中，MeT可以被重新使用作为对假单胞菌的抗毒力药物。版权所有 © 2023 Elsevier Ltd.

Metformin (MeT) is an FDA-approved drug with a myriad of health benefits. Besides being used as an anti-diabetic drug, MeT is also effective against various cancers, liver-, cardiovascular-, and renal diseases. This study was undertaken to examine its unique potential as an anti-virulence drug against an opportunistic bacterial pathogen, Pseudomonas aeruginosa. Due to the menace of multidrug resistance in pathogenic microorganisms, many novel or repurposed drugs with anti-virulence prospects are emerging as next-generation therapies with the aim to overshadow the application of existing antimicrobial regimens. The quorum sensing (QS) mechanisms of P. aeruginosa are an attractive drug target for attenuating bacterial virulence. In this context, the anti-QS potential of MeT was scrutinized using biosensor assays. MeT was comprehensively evaluated for its effects on different motility phenotypes, virulence factor production (phenotypic and genotypic expression) along with biofilm development in P. aeruginosa in vitro. At sub-lethal concentrations, MeT displayed prolific quorum quenching (QQ) ability and remarkably inhibited AHL biosynthesis in P. aeruginosa. Moreover, MeT (1/8 MIC) effectively downregulated the expression levels of various QS- and virulence genes in P. aeruginosa, which coincided with a notable reduction in the levels of alginate, hemolysin, pyocyanin, pyochelin, elastase, and protease production. In silico analysis through molecular docking also predicted strong associations between MeT and QS receptors of P. aeruginosa. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, MeT may be repurposed as an anti-virulence drug against P. aeruginosa in clinical settings.Copyright © 2023. Published by Elsevier Ltd.