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Early Effects of Rhodomyrtone on Membrane Integrity in Methicillin-Resistant Staphylococcus aureus
Wipawadee Sianglum1, Dennapa Saeloh2, Pongsri Tongtawe3
11 Department of Microbiology and Excellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University , Hat Yai, Thailand .
Abstract:
Strong evidence of high potency of rhodomyrtone as a promising antibacterial agent against pathogenic gram-positive bacteria has been clearly demonstrated in our previous work. The aim of this study was to provide insight into early action of rhodomyrtone, an acylphloroglucinol, on membrane damage in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA). Early effects of rhodomyrtone on the bacterial membrane integrity were detected in a time-course study. Flow cytometry revealed a reduction in green fluorescent emission and increase in uptake of propidium iodide in rhodomyrtone-treated bacterial cells in a concentration- and time-dependent manner. Disruption of cytoplasmic membrane was further monitored by measuring cellular adenosine triphosphate (ATP) and potassium ion (K+). Leakage of both ATP and K+ and significant decrease in intracellular ATP in MRSA were observed following treatment. Pronounced changes in the bacterial ultrastructure and morphology were confirmed by transmission electron microscopy and scanning electron microscopy. Bacterial cell disruption, holes in cell surface, and bulge formations were noted in rhodomyrtone-treated cells. In this study, we provided relevant data to clarify that rhodomyrtone is a bacterial cell membrane-damaging agent. A possible early effect of this novel compound involves bacterial membrane disruption.
Insights
Rhodomyrtone damages bacterial cell membranes, offering a new approach against drug-resistant bacteria. This study reveals its early membrane-disrupting effects on methicillin-resistant Staphylococcus aureus (MRSA).
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Previous work demonstrated rhodomyrtone's high potency against pathogenic gram-positive bacteria.
- Multidrug-resistant bacteria, like methicillin-resistant Staphylococcus aureus (MRSA), pose a significant global health threat.
Purpose of the Study:
- To investigate the early mechanisms of rhodomyrtone-induced membrane damage in MRSA.
- To elucidate the action of rhodomyrtone, an acylphloroglucinol, on bacterial membrane integrity.
Main Methods:
- Time-course studies using flow cytometry to assess membrane integrity.
- Measurement of intracellular adenosine triphosphate (ATP) and potassium ion (K+) leakage.
- Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) for ultrastructural analysis.
Main Results:
- Rhodomyrtone treatment led to increased propidium iodide uptake and reduced green fluorescent emission in MRSA cells in a dose- and time-dependent manner.
- Significant leakage of ATP and K+ from MRSA cells was observed, along with a decrease in intracellular ATP.
- Microscopy revealed bacterial cell disruption, surface holes, and bulge formations in rhodomyrtone-treated MRSA.
Conclusions:
- Rhodomyrtone acts as a bacterial cell membrane-damaging agent.
- The primary early effect of rhodomyrtone involves disruption of the bacterial membrane.
- Rhodomyrtone shows potential as a novel antibacterial agent targeting membrane integrity.
