Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is currently regarded as one of the most important drug-resistant pathogens causing nosocomial and community-acquired infections. Although berberine (BER) has shown anti-MRSA activity, the underlying mechanism is still unclear. In this study, the damage caused by BER on the cell surface of MRSA was systematically investigated by performing BER susceptibility test, determining K+ and alkaline phosphatase (ALP) release, detecting morphological alterations using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and ascertaining lipid profiles. The results showed that the minimum inhibitory concentration (MIC) of BER against MRSA252 was 128 μg/ml. Under the sub-MIC doses of BER, cell membrane permeability gradually increased in a dose-dependent manner, and 1 × MIC led to 43.8% higher K+ leakage and fourfold higher ALP secretion. The injuries on MRSA cell surface were further verified by SEM and TEM, and some cells displayed a doughnut-shaped structure. BER significantly altered the fatty acid species contents, including saturated fatty acids (C14:0, C15:0, C16:0, C18:0, and C20:0), and unsaturated fatty acids (C20:4, C20:1, and C18:1), indicating that BER compromised cell membrane integrity via lipid fluctuation. Thus, the findings of this study could help to unravel the molecular mechanism of BER against MRSA.
Highlights
The recent emergence and worldwide spread of multidrug-resistant bacteria have raised major public health concerns
Methicillin-resistant Staphylococcus aureus was identified as one of the global priority pathogens with antibiotic resistance by the World Health Organization (WHO) in 2017 (Tacconelli et al, 2018), and had attracted increasing concerns worldwide
The antimicrobial efficacy of BER against Methicillin-resistant Staphylococcus aureus (MRSA) was evaluated by biomass changes after BER treatment
Summary
The recent emergence and worldwide spread of multidrug-resistant bacteria have raised major public health concerns. Methicillin-resistant Staphylococcus aureus (MRSA), a main cause of nosocomial and community-acquired infections around the world (Hoffman and Outterson, 2015), have developed multidrug resistance and, have been responsible. Methicillin-resistant Staphylococcus aureus was identified as one of the global priority pathogens with antibiotic resistance by the World Health Organization (WHO) in 2017 (Tacconelli et al, 2018), and had attracted increasing concerns worldwide. Some natural antibiotic substances have been explored as candidates to control MRSA (Yu et al, 2005) Among these antibacterial agents, berberine (BER), one of the major components of berberine alkaloids from Coptis chinensis Franch, has been noted to show broad-spectrum antimicrobial activity against a variety of microorganisms (Wu et al, 2011), including MRSA (Luo et al, 2014). BER has been reported to display antimicrobial activity against almost all the tested MRSA strains, with minimum inhibitory concentrations (MIC) ranging from 32 to 128 μg/ml (Yu et al, 2005)
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