Exploring Eugenol as a Growth and Biofilm Inhibitor in <i>Leptospira interrogans</i> by a Combined Experimental and Computational Approach

Leptospira interrogans, known for its association with environmental biofilms, poses significant challenges in managing leptospirosis due to its persistent virulence and resistance to antimicrobial agents. Addressing the biofilms in infection and resistance necessitates novel anti-leptospiral agents and strategies, with bioactive compounds offering better biomolecules to combat leptospiral biofilms. This study investigates the role of eugenol against L. interrogans, which has been unexplored. In this study, we have evaluated the impact of eugenol on the growth and biofilm formation of L. interrogans. Eugenol inhibited 70% of biofilm formation at its MBIC70 (10 mM). These findings were further validated through fluorescence and scanning electron microscopy to assess cell viability and morphological changes. Furthermore, the expression levels of key genes, csrA and lipL32, associated with bacterial growth and biofilm formation, were analyzed using qRT-PCR. To complement these findings, molecular docking, c-DFT, and ADME profiles were performed to investigate the interaction of eugenol with the transpeptidase/penicillin-binding protein. The results strongly correlate with the biological outcomes observed in the experimental studies, supporting the efficacy of eugenol against L. interrogans.