Chadha, J.; Khullar, L.; Gulati, P.; Chhibber, S.; Harjai, K. Anti-Virulence Prospects of Metformin against Pseudomonas Aeruginosa: A New Dimension to a Multifaceted Drug. Microbial Pathogenesis 2023, 183, 106281, doi:10.1016/j.micpath.2023.106281.
Chadha, J.; Khullar, L.; Gulati, P.; Chhibber, S.; Harjai, K. Anti-Virulence Prospects of Metformin against Pseudomonas Aeruginosa: A New Dimension to a Multifaceted Drug. Microbial Pathogenesis 2023, 183, 106281, doi:10.1016/j.micpath.2023.106281.
Chadha, J.; Khullar, L.; Gulati, P.; Chhibber, S.; Harjai, K. Anti-Virulence Prospects of Metformin against Pseudomonas Aeruginosa: A New Dimension to a Multifaceted Drug. Microbial Pathogenesis 2023, 183, 106281, doi:10.1016/j.micpath.2023.106281.
Chadha, J.; Khullar, L.; Gulati, P.; Chhibber, S.; Harjai, K. Anti-Virulence Prospects of Metformin against Pseudomonas Aeruginosa: A New Dimension to a Multifaceted Drug. Microbial Pathogenesis 2023, 183, 106281, doi:10.1016/j.micpath.2023.106281.
Abstract
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. It has also been proven to demonstrate anti-ageing and neuroprotective effects. 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 the QS receptors of P. aeruginosa and MeT. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, the QQ, anti-virulence, and anti-fouling potential of MeT was elucidated for the first time against P. aeruginosa.
Keywords
Metformin; Quorum sensing; Quorum quenching; Pseudomonas aeruginosa; Virulence; Drug repurposing; Anti-virulence therapy; Biofilm inhibition
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
