AUTHOR=Sadik Ajmal , Viswaswar Jithin P. , Rajamoney Ambili , Rekha Anjali , Raj Darsana M. , Prakashan Deepthi , Vasudevan Mydhili , Visakh J. S. , Renuka Dhannya , Hely Sreetha , Shaji Sanu Korumadathil , Chandran Prakash R. , Kumar Geetha , Vijayan Nair Sobha , Haripriyan Jayalekshmi 

TITLE=Mitigation of quorum sensing mediated virulence factors of Pseudomonas aeruginosa: the role of Meldrum’s acid activated furan

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1272240

DOI=10.3389/fmicb.2023.1272240

ISSN=1664-302X

ABSTRACT=<p>The rapid emergence of drug resistant pathogens is a major threat which has warranted the development of alternative strategies to combat infectious diseases. In this work, we have tested the anti-virulent activity of Meldrum’s acid activated furan (MAF) and 1,3-dimethyl barbituric acid activated furan (BAF) against <italic>Chromobacterium violaceum</italic> and <italic>Pseudomonas aeruginosa</italic>. It was found that MAF significantly reduced the violacein production and biofilm formation of <italic>C. violaceum</italic> at sub-inhibitory concentrations. The quorum sensing (QS) regulated virulence factors of <italic>P. aeruginosa</italic> including biofilm formation, motility, pigment production, and elastase activity were also found to be reduced considerably at sub-inhibitory concentrations of MAF. Additionally, MAF downregulated the expression of genes in the QS circuitry of <italic>P. aeruginosa</italic>, demonstrating the potential of MAF in lowering the pathogenicity of <italic>P. aeruginosa</italic>. <italic>In silico</italic> studies demonstrated the potential of MAF to compete with the signaling molecules of <italic>C. violaceum</italic> and <italic>P. aeruginosa</italic> for the QS receptor interaction. <italic>In vivo</italic> studies using <italic>Caenorhabditis elegans</italic> demonstrated the anti-pathogenicity of MAF by enhancing the survival of <italic>P. aeruginosa</italic>-infected <italic>C. elegans</italic>. These results suggest that activated furan compounds could be potential inhibitors of QS-mediated virulence factors in <italic>C. violaceum</italic> and <italic>P. aeruginosa</italic>, encouraging their use in combating multidrug-resistant pathogens.</p>