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Increasing antibiotic-resistance in bacterial strains has boosted the need to find new targets for drug delivery. FtsA, a major bacterial divisome protein can be a potent novel drug-target. This study finds, morin (3,5,7,2′,4′-pentahydroxyflavone), a bio-available flavonoid, had anti-bacterial activities against Vibrio cholerae , IC 50 (50 μM) and MIC (150 μM). Morin (2 mM) kills ~20% of human lung fibroblast (WI38) and human intestinal epithelial (HIEC-6) cells in 24 h in-vitro. Fluorescence studies showed morin binds to VcFtsA (FtsA of V. cholerae) with a K d of 4.68 ± 0.4 μM, inhibiting the protein's polymerization by 72 ± 7% at 25 μM concentration. Morin also affected VcFtsA's ATPase activity, recording ~80% reduction at 20 μM concentration. The in-silico binding study indicated binding sites of morin and ATP on VcFtsA had overlapping amino acids. Mant-ATP, a fluorescent ATP-derivative, showed increased fluorescence on binding to VcFtsA in absence of morin, but in its presence, Mant-ATP fluorescence decreased. VcFtsA-S40A mutant protein did not bind to morin. VcFtsA–morin interaction inhibits the polymerization of the protein by affecting its ATPase activity. The destabilized VcFtsA assembly in-turn affected the cell division in V. cholerae , yielding an elongated morphology. Collectively, these findings explore the anti-bacterial effect of morin on V. cholerae cells targeting VcFtsA, encouraging it to become a potent anti-bacterial agent. Low cytotoxicity of morin against human cells (host) is therapeutically advantageous. This study will also help in synthesizing novel derivatives that can target VcFtsA more efficiently. [Display omitted] • Morin, a bioflavonoid, shows antibacterial activities with low cytotoxicity. • Morin targets a major cell division protein, FtsA, in Vibrio cholerae. • Morin binds to FtsA close to ATP binding site affecting the ATPase activity of FtsA and inhibiting its polymerization. • Inhibition of FtsA polymerization affects the cell division of Vibrio cholerae altering its morphology to an elongated one. • Morin could be a potent anti-bacterial agent against Vibrio cholerae. [ABSTRACT FROM AUTHOR] |
