Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting

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.

Efektivitas in vitro Alfa Mangostin Pada Pertumbuhan Bakteri Uropatogen Escherichia coli Multiresisten

“…Koh et al (2013) states that the α-mangostin bactericidal activity against in vitro can quickly reduce the bacterial colony to 103 5 minutes. Alpha mangostin damage the integrity of the cytoplasmic membrane of bacteria rapidly, causing damage in intracellular component bacteria and cause the bacteria to die.…”

Potency of Xanthone Derivatives as antibacterial agent against Methicillin-Resistant Staphylococcus Aureus (MRSA)

“…α-mangostin induces potential membrane disipation teice faster in two times Minimum Inhibitory Concentration (MIC), and thus causing a leakage of bacterial intracellular components. 37 Amphiphilic xanthone compound can disrupt bacterial membrane through a mechanism called interfacial activity model. 11 This mechanism depends on a balance between hidrophobik and electrostatic interaction of peptides, water, and lipid, and is also the basic mechanism of antimicrobial peptide/AMP.…”

“…Not only that it has high anti-MRSA activity, α-mangostin from G. mangostana (AM-0016) also has much lower hemolytic activity (membranolytic) in rabbit's eritrocytes thus it is not toxic to normal tissue. 37 The results from quantitative structure-activity relationship analysis of some modified α-mangostin group show that the substitution of N-ethyl group produces better inhibitory activity (MIC 0,39-3,125 µg/mL), while longer natural N-propyl or alkylamin substitution produce lesser anti MRSA activity, with MIC ≥ 12,5 µg/mL ( Table 3). The order of anti-MRSA activity and hemolytic is non isoprenyl or non hydrogenized compounds< hydrogenized isoprenyl < isoprenyl.…”

The EFFECT OF ALPHA-MANGOSTIN IN BALANCING THE RATIO OF CYTOKINES PRO-AND ANTI-INFLAMMATION-GAMMA (IFN-γ/IL-10) AND SEVERITY OF THE DISEASE IN MICE INFECTED WITH MYCOBACTERIUM TUBERCULOSIS MULTIDRUG-RESISTANT

“…The xanthones, α-and γ-mangostin, are major bioactive compounds found in fruit hulls of the mangostin [18]. α-mangostin has some pharmacological activities such as antioxidant [19], anti-TB [16,19], MTB-MDR [19,20], anti-inflammatory activities [21], pro-inflammatory activities [18], and increased the permeability of the bacterial cell membrane [22][23][24]. The compound α-mangostin is expected to contribute to the fight against and eliminate TB infection and MTB-MDR [16,19].…”