Benzoic acid derivatives as potent antibiofilm agents against Klebsiella pneumoniae biofilm

Abstract

Klebsiella pneumoniae is responsible for a significant proportion of human urinary tract infections, and its biofilm is a major virulence. One potential approach to controlling biofilm-associated infections is targeting the adhesin MrkD1P to disrupt biofilm formation. We employed Schrodinger's Maestro tool with the OPLS 2005 force field to dock compounds with the target protein. Two benzoic acid derivatives, 3-hydroxy benzoic acid and 2,5-dihydroxybenzoic acid, had strong binding free energies (-55.57 and -18.68 kcal/mol) and were the most potent compounds. The in-vitro experiments were conducted to validate the in-silico results. The results showed that both compounds effectively inhibited biofilm formation at low concentrations (4 and 8 mg/mL, respectively) and had antibiofilm activity, restricting cell attachment. Both compounds demonstrated a strong biofilm inhibitory effect, with 97% and 89% reduction in biofilm by 3-hydroxy benzoic acid and 2,5-dihydroxybenzoic acid, respectively. These findings suggest that natural compounds can be a potential source of new drugs to combat biofilm-associated infections. The study highlights the potential of targeting adhesin MrkD1P as an effective approach to controlling biofilm-associated infections caused by K. pneumoniae. The results may have implications for the development of new therapies for biofilm-associated infections and pave the way for future research in this area.

Keywords: Benzoic acid; Biofilm; Klebsiella pneumoniae; MrkD1P; Natural compounds.