Natural flavonoid morin showed anti-bacterial activity against Vibrio cholera after binding with cell division protein FtsA near ATP binding site.

Abstract

BACKGROUND\nIncreasing 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.\n\n\nMETHODS AND RESULTS\nThis study finds, morin (3,5,7,2 ,4 -pentahydroxyflavone), a bio-available flavonoid, had anti-bacterial activities against Vibrio cholerae, IC50 (50\u202fμM) and MIC (150\u202fμM). Morin (2\u202fmM) kills ~20% of human lung fibroblast (WI38) and human intestinal epithelial (HIEC-6) cells in 24\u202fh in-vitro. Fluorescence studies showed morin binds to VcFtsA (FtsA of V. cholerae) with a Kd of 4.68\u202f±\u202f0.4\u202fμM, inhibiting the protein s polymerization by 72\u202f±\u202f7% at 25\u202fμM concentration. Morin also affected VcFtsA s ATPase activity, recording ~80% reduction at 20\u202fμM 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.\n\n\nCONCLUSIONS\nVcFtsA-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.\n\n\nGENERAL SIGNIFICANCE\nCollectively, 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.