Gramine disrupts quorum sensing and biofilm formation of Pseudomonas aeruginosa: An integrated experimental and computational analysis
摘要
Bacterial resistance towards antibiotics has become a major problem worldwide. Bacteria become more resistant towards available antibiotics due to quorum sensing and biofilm formation. Alkaloids exhibited potential anti-bacterial activity. In the present study, the anti-quorum sensing and antibiofilm abilities of gramine (GRM) are evaluated. Gramine, an alkaloid already reported for several biological activities includes antiviral, anti-bacterial and antitumor was evaluated for its inhibition of quorum sensing and biofilm mediated virulence in Pseudomonas aeruginosa. The anti-infective effect of GRM using Caenorhabditis elegans and Galleria mellonella models was determined. Gramine reduced violacein production by 78% in C. violaceum. GRM inhibit 84% biofilm formation in P. aeruginosa. Notably, GRM inhibits several virulence factors (Pyocyanin, Pyoverdine, HCN, Alginate and several others) of P. aeruginosa. Further validation by qRT-PCR showed that GRM significantly downregulated several virulence associated genes. In silico studies revealed the GRM interaction with the three main quorum sensing signal receptors (LasR, RhlR and PqsR) of P. aeruginosa. In vivo anti-infective experiments suggested GRM’s protective effect in C. elegans and G. mellonella infection models. Our results suggests that GRM as an effective anti-biofilm and anti-infective agent.
Graphical abstract