Trans-Cinnamaldehyde Inhibitory Activity Against mrkA, treC, and luxS Genes in Biofilm-forming Klebsiella pneumoniae: An In Silico Study

Abstract

Biofilm-forming Klebsiella pneumoniae is a multidrug resistant organism that causes severe infections in humans. The   luxS, treC and mrkA genes play a significant role in the formation of K. pneumoniae biofilms. Cinnamaldehyde has been  shown to exhibit antimicrobial and antibiofilm activities against pathogenic bacteria. The present study aims to  investigate the antibiofilm activity of cinnamaldehyde in silico. In silico study was done using Autodock Vina software  and pharmacokinetics prediction using the pkCSM strategy. The ability of cinnamaldehyde to inhibit the mrkA, treC, and   luxS genes of K. pneumonia was accessed by docking the 3D structure of cinnamaldehyde with the luxS, mrkA, and treC  gene receptors. Post-docking analysis such as binding affinities, hydrophobic interactions, and pharmacokinetic  predictions were carried out. Cinnamaldehyde showed low binding affinities for the three genes; luxS (-5.6 kcal/mol),   mrkA (-5.0 kcal/mol), and treC (-6.0 kcal/mol). The root mean square deviation (RMSD) values were found to be 1.461,  1.210, and 1.426 for luxS, mrkA, and treC gene receptors, respectively. Cinnamaldehyde had a number of hydrophobic  interactions as seen in the ligand-receptor interactions for luxS (Lys 13; Asn 15; His 11; Pro 43; Leu 159; and Val 9), mrkA  (Phe 157; Ala 162; and Lys 129). Cinnamaldehyde had high bond-free energy similar to that of ciprofloxacin docked with  the same gene receptor. From the pharmacokinetics predictions, cinnamaldehyde had a good pharmacokinetics profile.  In conclusion, cinnamaldehyde has a high docking score comparable to ciprofloxacin and therefore has a potential for  use as antibacterial and antibiofilm agent against Klebsiella pneumoniae.