Evaluation of carvacrol and quercetin against surgical site infection pathogen Escherichia coli: In silico target identification, anti-biofilm efficacy, and cellular safety

Surgical site infections (SSIs) are postoperative complications driven by biofilm development on surgical wounds or implanted medical equipment. SSIs create a risk in terms of morbidity, extended hospitalization, and in extreme cases may cause mortality. The multi-drug-resistant bacteria, which frequently exist as poly-microbial communities in biofilms, present multiple tolerance mechanisms that render SSIs extremely difficult to treat with standard antibiotics. Besides, biofilm development relies on genes/proteins which act as master regulators governing biofilm assembly. Thus, targeting these regulatory switches can effectively curb biofilm development. Phytochemicals have come up as a likely option that can be effective against biofilm-forming multi drug-resistant bacteria by interacting with biofilm forming master regulators. In this study, in silico approaches were implemented to compare the interacting efficiency of different phytochemicals on a master biofilm regulator protein in Escherichia coli (E. coli), a common SSI pathogen. Validation of the most potent phytochemicals after analyzing the in silico results were carried out under in vitro settings to confirm their antibacterial and antibiofilm potential against biofilm-forming bacteria. Furthermore, in vitro safety assessments on human embryonic kidney cells (HEK-293) demonstrated minimal cytotoxicity, confirming the bio-compatibility of the phytochemicals at the therapeutic concentrations. Thus, targeting central biofilm regulators with non-toxic phytochemicals may to reduce the incidence of biofilm associated infections in post-surgery patients.