Natural flavonoid morin showed anti-bacterial activity against Vibrio cholera after binding with cell division protein FtsA near ATP binding site.
Biochim Biophys Acta Gen Subj
; 1865(8): 129931, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34023444
ABSTRACT
BACKGROUND:
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. METHODS ANDRESULTS:
This study finds, morin (3,5,7,2',4'-pentahydroxyflavone), a bio-available flavonoid, had anti-bacterial activities against Vibrio cholerae, IC50 (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 Kd 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.CONCLUSIONS:
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. GENERALSIGNIFICANCE:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Vibrio cholerae
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Flavonoides
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Regulação Bacteriana da Expressão Gênica
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Trifosfato de Adenosina
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article