Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G
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 an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016420301778 |
| _version_ | 1818340872544059392 |
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| author | Petruta Aelenei Cristina Mihaela Rimbu Cristina Elena Horhogea Andrei Lobiuc Anca-Narcisa Neagu Simona Isabela Dunca Iuliana Motrescu Gabriel Dimitriu Ana Clara Aprotosoaie Anca Miron |
| author_facet | Petruta Aelenei Cristina Mihaela Rimbu Cristina Elena Horhogea Andrei Lobiuc Anca-Narcisa Neagu Simona Isabela Dunca Iuliana Motrescu Gabriel Dimitriu Ana Clara Aprotosoaie Anca Miron |
| author_sort | Petruta Aelenei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:49:48Z |
| format | Article |
| id | doaj.art-e5d2c6e033ed4e908ed02984cbc92560 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-12-13T15:49:48Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-e5d2c6e033ed4e908ed02984cbc925602022-12-21T23:39:33ZengElsevierSaudi Pharmaceutical Journal1319-01642020-10-01281011721181Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon GPetruta Aelenei0Cristina Mihaela Rimbu1Cristina Elena Horhogea2Andrei Lobiuc3Anca-Narcisa Neagu4Simona Isabela Dunca5Iuliana Motrescu6Gabriel Dimitriu7Ana Clara Aprotosoaie8Anca Miron9Department 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, RomaniaDepartment 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, RomaniaDepartment 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; Corresponding author.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, RomaniaFaculty of Biology, Alexandru Ioan Cuza University of Iasi, Carol I Bd. 20A, Iasi 700505, RomaniaFaculty of Biology, Alexandru Ioan Cuza University of Iasi, Carol I Bd. 20A, Iasi 700505, RomaniaScience 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, RomaniaDepartment of Medical Informatics and Biostatistics, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, RomaniaDepartment of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, RomaniaDepartment of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Str. 16, Iasi 700115, RomaniaCombination 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.http://www.sciencedirect.com/science/article/pii/S1319016420301778MorusinKuwanon GAntibioticsAntibacterial synergyMRSAMembrane permeabilization |
| spellingShingle | Petruta Aelenei Cristina Mihaela Rimbu Cristina Elena Horhogea Andrei Lobiuc Anca-Narcisa Neagu Simona Isabela Dunca Iuliana Motrescu Gabriel Dimitriu Ana Clara Aprotosoaie Anca Miron Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G Saudi Pharmaceutical Journal Morusin Kuwanon G Antibiotics Antibacterial synergy MRSA Membrane permeabilization |
| title | Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G |
| title_full | Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G |
| title_fullStr | Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G |
| title_full_unstemmed | Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G |
| title_short | Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G |
| title_sort | prenylated phenolics as promising candidates for combination antibacterial therapy morusin and kuwanon g |
| topic | Morusin Kuwanon G Antibiotics Antibacterial synergy MRSA Membrane permeabilization |
| url | http://www.sciencedirect.com/science/article/pii/S1319016420301778 |
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