Development of novel strategies against the threats of drug-resistant Escherichia coli: an in silico and in vitro investigation.

Escherichia coli (E. coli) biofilms pose alarming threats in healthcare due to their invulnerability to drug therapy. Stand-alone therapies of antimicrobial compounds/antibiotics are not particularly effective against those resistant strains. However, combination therapy of compounds could be used to deal with such threats. Towards this direction, the natural compound cuminaldehyde was employed in combination with the aminoglycoside antibiotic tobramycin to target the biofilm-forming multidrug-resistant (MDR) clinical strains of E. coli, which were isolated from urine samples of patient's at Suraksha Diagnostic Private Limited (Kolkata, India). At first, an integrated in silico approach (PASS online, Swiss ADME, PROTOX 3.0, and OSIRIS) was explored to predict the potential biological activities, and other relevant pharmacokinetic parameters of cuminaldehyde and tobramycin. The in silico analysis suggested that tobramycin might not be bioavailable orally due to its molecular size, polarity, and poor GI absorption. However, cuminaldehyde was well absorbed in the GI but could cause irritation if swallowed in LD50 amounts. Further, in vitro assessments were performed to analyse the antimicrobial and antibiofilm activity of both compounds, alone and in combination, against clinical strains of E. coli. The results suggested that cuminaldehyde and tobramycin together could show an additive effect against the clinical strains of E. coli. The combination of the compounds showed a substantial decrease in minimum inhibitory concentration (MIC) and biofilm formation compared to individual application. The present study indicates that combinatorial application involving cuminaldehyde and tobramycin could inhibit the formation of biofilms in E. coli, potentially aiding in the management of microbial infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04246-0.