Benzyl isocyanate isolated from the leaves of <i>Psidium guajava</i> inhibits <i>Staphylococcus aureus</i> biofilm formation

Abstract

Benzyl isocyanate (BIC), from methanol extract of <i>Psidium guajava</i> leaves, exhibited substantial anti-biofilm activities against <i>Staphylococcus aureus</i>, the common bacterial pathogen in nosocomial infections. Major components of the extract included eugenol, BIC, phenyl-2-methoxy-4-(1-propenyl)-acetate and 2,5-pyrrolidinedione,1-penta-3-4-dienyl, analyzed by GC-MS and HPLC studies. BIC exhibited substantial anti-biofilm activitiy against <i>S. aureus</i>, established by assaying biofilm formation, biofilm metabolic activity, bacterial adherence to hydrocarbons, exopolysaccharide formation, and optical and scanning electron microscopic studies. BIC significantly downregulated the important biofilm markers of <i>S. aureus</i>, <i>viz., ica</i>AD, <i>sar</i>A and <i>agr</i>, observed by quantitative real time polymerase chain reaction analysis. Molecular docking studies revealed thermodynamically favorable interaction of BIC with IcaA, SarA and Agr, having Gibbs energy values of -8.45, -9.09 and -10.29 kcal mol^-1, respectively. BIC after binding to IcaR, the repressor of IcaA, influences its binding to target DNA site (<i>E</i>_shape, -157.27 kcal mol^-1). The results are considered to demonstrate anti-biofilm potential of BIC against bacterial infections.