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Ethyl Acetate Extracts of Edible Mushroom Species Enhance β-Lactam Activity Against an MRSA Isolate in vitro
James Blee1, Peter O'Hara1, Thomas Smyth1
1Department of Health and Nutritional Science, Atlantic Technological University, Sligo, Ireland.
Research Background:
The rapid emergence of antimicrobial resistance (AMR) has led to numerous pathogens developing resistance to available antibiotics. Staphylococcus aureus is a leading cause of hospital-acquired infections, and the emergence of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) has led to increased clinical complications and higher mortality rates. As such, restoration of first-line β-lactam antibiotic activity is a viable strategy to combat AMR. The antimicrobial activity of edible mushroom extracts is well reported; however, their use as a source of antibiotic modulators is relatively unexplored, and current reports often do not adhere to drug combination guidelines. The aim of this study is to evaluate the potential of extracts derived from ten edible mushroom species to modulate β-lactam antibiotics against MRSA with reference to the recommended guidelines.
Experimental Approach:
Antimicrobial activity (minimum inhibitory concentration (MIC)) and antibiotic-modulating activity (fractional inhibitory concentration index (FICI)) were assessed using the broth microdilution method. The cell viability assay was used to assess cell membrane integrity following treatment to offer insight into potential mechanisms of action.
Results And Conclusions:
Both antimicrobial and antibiotic modulatory activity were found only in ethyl acetate extracts. Hericium erinaceus extract showed the strongest antimicrobial activity against S. aureus (MIC=0.8 mg/mL), while Agaricus bisporus extract exhibited the strongest antibiotic-modulating properties, exhibiting a 25-fold reduction in the MIC of ampicillin, amoxicillin and penicillin against an MRSA isolate (FICI=0.29), indicating synergism. The mechanism of action indicates reduced cell membrane integrity, which may increase intracellular antibiotic concentration.
Novelty And Scientific Contribution:
These results indicate the potential use of ethyl acetate extracts from edible mushrooms, specifically A. bisporus, as a source of antibiotic-modulating compounds. To our knowledge, this is the first study to evaluate the antibiotic-modulating effects of H. erinaceus, Hypsizygus tessulatus and Pholiota adiposa. This study also highlights the necessity to adhere to FICI guidelines when evaluating the antibiotic-modulating potential of edible mushroom extracts.
Insights
Edible mushroom extracts, particularly from Agaricus bisporus, show potential to restore antibiotic effectiveness against resistant bacteria like MRSA. This study highlights their antibiotic-modulating properties and novel mechanisms.
Area of Science:
- Microbiology
- Pharmacology
- Natural Products Chemistry
Background:
- Antimicrobial resistance (AMR) is a growing global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) causing severe hospital-acquired infections.
- Restoring the efficacy of first-line β-lactam antibiotics is a critical strategy to combat AMR.
- Edible mushroom extracts are recognized for antimicrobial properties, but their potential as antibiotic modulators, especially against MRSA, remains underexplored and often lacks adherence to drug combination guidelines.
Purpose of the Study:
- To investigate the potential of extracts from ten edible mushroom species to modulate β-lactam antibiotics against MRSA.
- To evaluate these extracts based on established drug combination guidelines, specifically the fractional inhibitory concentration index (FICI).
- To explore the potential mechanisms of action of the active mushroom extracts.
Main Methods:
- Broth microdilution method was employed to determine minimum inhibitory concentration (MIC) for antimicrobial activity and fractional inhibitory concentration index (FICI) for antibiotic-modulating activity.
- Cell viability assays were conducted to assess the impact on cell membrane integrity.
- Ethyl acetate extracts were prioritized for further analysis due to preliminary findings.
Main Results:
- Ethyl acetate extracts from edible mushrooms demonstrated both antimicrobial and antibiotic-modulating activities.
- Hericium erinaceus extract exhibited the strongest antimicrobial effect against Staphylococcus aureus (MIC=0.8 mg/mL).
- Agaricus bisporus extract showed significant antibiotic-modulating properties, reducing the MIC of ampicillin, amoxicillin, and penicillin against an MRSA isolate by 25-fold (FICI=0.29), indicating synergistic effects. This suggests disruption of cell membrane integrity.
Conclusions:
- Ethyl acetate extracts from edible mushrooms, particularly Agaricus bisporus, are promising sources of compounds that can modulate β-lactam antibiotics against MRSA.
- This study provides the first evaluation of antibiotic-modulating effects for Hericium erinaceus, Hypsizygus tessulatus, and Pholiota adiposa extracts.
- Adherence to FICI guidelines is crucial for accurately assessing the antibiotic-modulating potential of natural product extracts.
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