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|Title:||Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting||Authors:||Koh, J.-J.
|Issue Date:||Feb-2013||Citation:||Koh, J.-J., Qiu, S., Zou, H., Lakshminarayanan, R., Li, J., Zhou, X., Tang, C., Saraswathi, P., Verma, C., Tan, D.T.H., Tan, A.L., Liu, S., Beuerman, R.W. (2013-02). Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting. Biochimica et Biophysica Acta - Biomembranes 1828 (2) : 834-844. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bbamem.2012.09.004||Abstract:||The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created the need for better therapeutic options. In this study, five natural xanthones were extracted and purified from the fruit hull of Garcinia mangostana and their antimicrobial properties were investigated. α-Mangostin was identified as the most potent among them against Gram-positive pathogens (MIC = 0.78-1.56 μg/mL) which included two MRSA isolates. α Mangostin also exhibited rapid in vitro bactericidal activity (3-log reduction within 5 min). In a multistep (20 passage) resistance selection study using a MRSA isolated from the eye, no resistance against α-mangostin in the strains tested was observed. Biophysical studies using fluorescence probes for membrane potential and permeability, calcein encapsulated large unilamellar vesicles and scanning electron microscopy showed that α mangostin rapidly disrupted the integrity of the cytoplasmic membrane leading to loss of intracellular components in a concentration-dependent manner. Molecular dynamic simulations revealed that isoprenyl groups were important to reduce the free energy for the burial of the hydrophobic phenyl ring of α-mangostin into the lipid bilayer of the membrane resulting in membrane breakdown and increased permeability. Thus, we suggest that direct interactions of α-mangostin with the bacterial membrane are responsible for the rapid concentration- dependent membrane disruption and bactericidal action. © 2012 Elsevier B.V. All rights reserved.||Source Title:||Biochimica et Biophysica Acta - Biomembranes||URI:||http://scholarbank.nus.edu.sg/handle/10635/101518||ISSN:||00052736||DOI:||10.1016/j.bbamem.2012.09.004|
|Appears in Collections:||Staff Publications|
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