Carvacrol, a monoterpenoid, binds quorum sensing proteins (LasI and LasR) and swarming motility protein BswR of <i>Pseudomonas aeruginosa,</i> resulting in loss of pathogenicity: an in silico approach
Susmita Datta, Vishal Singh, Soma Nag, Dijendra Nath Roy
Abstract
The pathogenic Pseudomonas aeruginosa utilizes a quorum-sensing pathway for biofilm formation. The quorum-sensing proteins LasI and LasR of the Las system, alongside the swarming motility protein BswR, play a crucial role in the biofilm-mediated antibiotic resistance phenomenon. In this in silico study, LasI, LasR, and BswR were the prime targets for binding studies by promising drug candidates like linalool, ferutinin, citronellal, and carvacrol. These monoterpenoid compounds are carefully considered for this study due to their reported anti-microbial activity. Among all, carvacrol exhibited the highest binding energies with LasI (−5.932 kcal/mol), LasR (−7.469 kcal/mol), and BswR (−4.42 kcal/mol). Furthermore, the MMGBSA scores between carvacrol and LasI, LasR, and BswR individually are −33.14, −54.22, and −41.86 kcal/mol, which further corroborated the strong binding. During 100 ns of simulation, the ligand binds to the active sites of these proteins through the H-bonds at Ile107 of LasI, Tyr47 of LasR, and Leu57 of BswR. In addition, the root-mean-square deviation values of the ligand-protein complex are within the appropriate range of less than 5 Å. Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis confirmed that carvacrol has the most negligible toxicity to mammalian cells. Hence, this finding is the first report to show that carvacrol can inhibit the Pseudomonas aeruginosa biofilms.