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Rapid Bactericidal Action of Alpha-mangostin Against MRSA as an Outcome of Membrane Targeting.
MedLine Citation:
PMID:  22982495     Owner:  NLM     Status:  Publisher    
The emergence of methicillin-resistance 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 amongst them against Gram-positive pathogens (MIC=0.78 - 1.56μg/mL) which included two MRSA isolates. α mangostin also exhibited rapid in vitro bactericidal activity (3-log reduction within 5minutes). In a multistep (20 passage) resistance selection study using a MRSA isolated from the eye, there was no resistance against α-mangostin in the strains tested were 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.
Jun-Jie Koh; Shengxiang Qiu; Hanxun Zou; Rajamani Lakshminarayanan; Jianguo Li; Xiaojun Zhou; Charles Tang; Padmanabhan Saraswathi; Chandra Verma; Donald T H Tan; Ai Ling Tan; Shouping Liu; Roger W Beuerman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-13
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074. Electronic address:
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