Biofilm reduction, in-vitro cytotoxicity and computational drug-likeness of selected phytochemicals to combat multidrug-resistant bacteria

Abstract

Multidrug-resistant (MDR) bacteria in biofilms are frequently linked with persistent infections across healthcare settings, due to their virulence factors. Since the post-antibiotic era coerces the quest for novel therapeutics, the use of medicinal plants and their phytochemicals emerges as prospective alternatives for the failing antibiotics. Preliminary screening of untargeted drugs for their drug-likeness and biosafety properties is a necessary step in the advancement of the drug discovery process. Thus, the study aimed to assess the noteworthy phytochemicals with antibacterial potential to reduce the biofilm formation of selected MDR bacteria, evaluate their safe use and drug-likeness properties thereby providing advanced knowledge to contribute to the search for safe, antipathogenic drugs. Three phytochemicals of 1,2,3-benzenetriol, guanosine and phytol revealed significant minimum inhibitory concentrations (MIC) between 0.250 – 0.040 mg/mL against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes. Guanosine and phytol, both revealed noteworthy MIC values of 0.016 and 0.031 mg/mL for S. pyogenes and S. aureus, respectively. Five MDR bacterial pathogens treated with 1,2,3-benzenetriol, guanosine and phytol at a concentration of 0.250 mg/mL reduced anti-adhesion and biofilm development up to 78.88% and 31.82%, respectively. In situ visualisation by scanning electron microscope (SEM) displayed guanosine to significantly disrupt the biofilm structures of S. aureus, S. pyogenes and P. aeruginosa. Atomic force microscope (AFM) detected differences between the topographies of S. aureus, S. pyogenes and P. aeruginosa biofilms treated with guanosine and phytol. Guanosine and phytol showed approximately 100% of cell viability in a dose-dependent manner (0.25 – 0.001 mg/mL) while causing no cell damage on African monkey kidney Vero (epithelial) cells and showed a cytostatic rather than a cytotoxic effect. Drug-likeness in-silico screening revealed that the compounds obeyed Lipinski's rules and have bioavailable scores of 0.55F. Guanosine and phytol showed antivirulent, biosafety and drug-likeness properties with significant pharmacokinetic predictions. This study highlights the significance of phytotherapeutics for the development of novel antipathogenic agents.