Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G

Abstract

Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis . Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4–512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis . At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G . Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.

The Impact of Salinity Stress on Antioxidant Response and Bioactive Compounds of Nepeta cataria L.

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The Pro-Health Benefits of Morusin Administration—An Update Review

“…The newest research indicates that morusin may be used for the development of combination antimicrobial therapies. Aelenei et al [ 55 ] confirmed that morusin increases antibiotic activity and reverses antibiotic resistance in S. aureus and S. epidermidis .…”

Preparation, characterization, and antibacterial activity of plaunotol and plaunoi extracts complexed with hydroxypropyl-β-cyclodextrin

“…Among the systemic antibacterial agents, topical clindamycin (1% w/w) is usually prescribed for acne vulgaris ( Zaenglein et al, 2016 ). Although combination therapy involving herbal drug products and antibiotics has been proposed as a strategy to improve healing and combat antibiotic resistance ( Martin and Ernst, 2003 , Chanda and Baravalia, 2010 , Aelenei et al, 2020 ). The hydrogel containing aloe gel, mangosteen rind, and green tea leaf extract reportedly improved total acne lesion and severity better than the commercial 1% clindamycin gel ( Waranuch et al, 2019 ).…”