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

Autor:	Aelenei P; Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, Romania.; Regulatory Affairs Department, Fiterman Pharma LLC, Pacurari Road 127, Iasi 700544, Romania., Rimbu CM; Department of Public Health, Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Agricultural Sciences and Veterinary Medicine of Iasi, Mihail Sadoveanu Al. 8, Iasi 700489, Romania., Horhogea CE; Department of Public Health, Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Agricultural Sciences and Veterinary Medicine of Iasi, Mihail Sadoveanu Al. 8, Iasi 700489, Romania., Lobiuc A; Human Health and Development Department, Stefan cel Mare University of Suceava, Universitatii Str. 13, Suceava 720229, Romania.; Integrated Research Centre for Environmental Studies in the N-E Area - CERNESIM, L2 Laboratory, Alexandru Ioan Cuza University of Iasi, Carol I Bd. 20A, Iasi 700506, Romania., Neagu AN; Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Carol I Bd. 20A, Iasi 700505, Romania., Dunca SI; Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Carol I Bd. 20A, Iasi 700505, Romania., Motrescu I; Science Department & Research Institute for Agriculture and Environment, Ion Ionescu de la Brad University of Agricultural Sciences and Veterinary Medicine of Iasi, Mihail Sadoveanu Al. 3, Iasi 700490, Romania., Dimitriu G; Department of Medical Informatics and Biostatistics, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, Romania., Aprotosoaie AC; Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, Romania., Miron A; Department of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, Romania.
Jazyk:	angličtina
Zdroj:	Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society [Saudi Pharm J] 2020 Oct; Vol. 28 (10), pp. 1172-1181. Date of Electronic Publication: 2020 Aug 18.
DOI:	10.1016/j.jsps.2020.08.006
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. (© 2020 The Author(s).)
Databáze:	MEDLINE
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