MORUSIN AND KUWANON G – PROMISING ANTI-MRSA AGENTS

Authors

  • Petruta AELENEI “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania
  • Cristina Elena HORHOGEA “Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine of Iasi
  • Cristina Mihaela RIMBU Regulatory Affairs Department, Fiterman Pharma LLC, Iasi, Romania
  • G. DIMITRIU “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania
  • Ana Clara APROTOSOAIE “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania
  • Anca MIRON “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

Abstract

MORUSIN AND KUWANON G-PROMISING ANTI-MRSA AGENTS (Abstract): Synergy between natural products and antibiotics represent a promising strategy in the development of new antimicrobial therapies. Aim: The present work investigated possible synergistic interactions between prenylated flavones morusin and kuwanon G and antibiotics (tetracycline, ciprofloxacin) against methicillin-resistant Staphylococcus aureus (MRSA). Material and Methods: The minimum inhibitory concentrations (MICs) of prenylated flavones and antibiotics against MRSA (MRSA ATCC 33591 and four MRSA isolates of animal origin) were determined by the broth microdilution method. The interactions between prenylated flavones and antibiotics were evaluated by the checkerboard and time-kill assays. Results: In the broth microdilution assay, morusin and kuwanon G showed very good antibacterial activity (MICs ranging 3.13 and 12.50 µg/mL). The checkerboard assay demonstrated that morusin and kuwanon G act synergistically with both antibiotics; significant reductions in antibiotic MICs (2 to 512-fold) were recorded. The time-kill assay (at ½MIC) indicated bactericidal synergy for the combinations of morusin or kuwanon G with ciprofloxacin against S. aureus ATCC 33591. Conclusions: The combination of morusin or kuwanon G with antibiotics are good candidates for the development of novel treatments for MRSA infections in humans and animals.

Author Biographies

  • Petruta AELENEI, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Pharmacy,
    Department of Pharmaceutical Sciences (II)
    Regulatory Affairs Department, Fiterman Pharma LLC, Iasi, Romania

  • Cristina Elena HORHOGEA, “Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine of Iasi

    Faculty of Veterinary Medicine
    Department of Public Health

  • G. DIMITRIU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Medicine
    Department of Preventive Medicine and Interdisciplinarity

  • Ana Clara APROTOSOAIE, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Pharmacy,
    Department of Pharmaceutical Sciences (II)

  • Anca MIRON, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Pharmacy,
    Department of Pharmaceutical Sciences (II)

References

1. Gaur R, Gupta VK, Singh P, Pal A, Darokar MP, Bhakuni RS. Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin Isolated from Glycyrrhiza glabra Against Methicillin-Resistant Staphylococcus aureus (MRSA). Phytother Res 2016; 30: 1708-1715.
2. Dorneanu OS, Luncă C, Năstase E.V, Tuchiluş CG, Vremeră T, Iancu LS. Detection of aminoglycoside and macrolide resistance mechanisms in methicillin-resistant Staphylococcus aureus. Rev. Med. Chir. Soc. Med. Nat. Iaşi 2016; 120: 886-891.
3. Tucaliuc D, Alexa O, Tuchiluş CG, Ursu RG, Tucaliuc ES, Iancu LS. Analysis of antibiotic resistance pattern of S. aureus strains isolated from the orthopedics–traumatology section of “Sf. Spiridon” County Clinical Emergency Hospital, Iaşi. Rev. Med. Chir. Soc. Med. Nat. Iaşi 2014; 118: 780-787.
4. Petinaki E, Spiliopoulou I. Methicillin-resistant Staphylococcus aureus colonization and infection risks from companion animals: current perspectives. Vet Med 2015; 6: 373-382.
5. Nienhoff U, et al. Transmission of methicillin-resistant Staphylococcus aureus strains between humans and dogs: two case reports. J Antimicrob Chemother 2009; 64: 660-662.
6. Wendlandt S, et al. Resistance phenotypes and genotypes of methicillin-resistant Staphylococcus aureus isolates from broiler chickens at slaughter and abattoir workers. J Antimicrob Chemother 2013; 68: 2458-2463.
7. Bramble M, Morris D, Tolomeo P, Lautenbach E. Potential Role of Pet Animals in Household Transmission of Methicillin-Resistant Staphylococcus aureus: A Narrative Review. Vector Borne Zo-onotic Dis 2011; 11: 617-620.
8. Marshall BM, Levy SB. Food Animals and Antimicrobials: Impacts on Human Health. Clin Microbiol Rev 2011; 24: 718-733.
9. Xiaohua Ye, et al. Genotypic and Phenotypic Markers of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC9 in Humans. Appl Environ Microbiol 2016; 82: 3892-3899.
10. Mehndiratta PL and Bhalla P. Use of antibiotics in animal agriculture & emergence of methicillin-resistant Staphylococcus aureus (MRSA) clones: Need to assess the impact on public health. Indian J Med Res 2014; 140: 339-344.
11. van Vuuren S and Viljoen A. Plant-Based Antimicrobial Studies – Methods and Approaches to Study the Interaction between Natural Products. Planta Med 2011; 77: 168-1182.
12. Mazimba O, Majinda RRT, Motlhank D. Antioxidant and antibacterial constituents from Morus nigra. Afr. J. Pharm. Pharmacol 2011; 5: 751-754.
13. Guo H, et al. Kuwanon G Preserves LPS-Induced Disruption of Gut Epithelial Barrier In Vitro. Mole-cules 2016; 21: 1597.
14. Pang D, et al. Antibacterial activity of 10 phenolic compounds from mulberry. J. Chin. Pharm. Univ 2014; 45: 221-226.
15. Sohn HY, Son KH, Kwon CS, Kwon GS, Kang SS. Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai. Phy-tomedicine 2004; 11: 666-672.
16. Abalaşei I. Studies Regarding the Laboratory Diagnosis, Classical and Nonconventional Therapy of Dermatitis with Bacterial Substrate in Dogs and Cats. Ph.D. Thesis 2018; University of Agricultural Sciences and Veterinary Medicine of Iasi, Romania.
17. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute, 2017.
18. European Committee on Antimicrobial Susceptibility Testing. Testing Breakpoint tables for interpre-tation of MICs and zone diameter Version 7.0. 2017.
19. Segatore B, et al. In vitro interaction of usnic acid in combination with antimicrobial agents against methicillin-resistant Staphylococcus aureus clinical isolates determined by FICI and E model methods. Phytomedicine 2012; 19: 341-347.
20. Mulyaningsih S, Sporer F, Zimmermann S, Reichling J, Wink M. Synergistic properties of the terpe-noids aromadendrene and 1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens. Phytomedicine 2010; 17: 1061-1066.
21. Meletiadis J, Verweij PE, TeDorsthorst DT, Meis JF, Mouton JW. Assessing in vitro combinations of antifungal drugs against yeasts and filamentous fungi: comparison of different drug interaction models. Med Mycol 2005; 43: 133-152.
22. Zuo GY, Wang CJ, Han J, Li YQ, Wang GC. Synergism of coumarins from the Chinese drug Zan-thoxylum nitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). Phytomedicine 2016; 23: 1814-1820.
23. Rîmbu CM, et al. The antibacterial activity and synergies between morusin and some antibiotics against MRSA strains-preliminary study. Lucrări ştiinţifice. Seria Medicină Veterinară Iasi 2017; 60: 41-49.
24. Horhogea C, et al. The antibacterial activity of kuwanon G and its interactions with antibiotics against MRSA strains-preliminary study. Lucrări ştiinţifice. Seria Medicină Veterinară Iasi 2017; 60: 32-40.
25. Zuo GY, Yang CX, Han J, Li YQ, Wang GC. Synergism of prenylflavonoids from Morus alba root bark against clinical MRSA isolates. Phytomedicine 2018; 39: 93-99.

Additional Files

Published

2019-03-29

Issue

Vol. 123 No. 1 (2019): The Medical-Surgical Journal

Section

PHARMACY

License

COPYRIGHT 
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.

COPYRIGHT TRANSFER FORM FOR 

REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /

THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI

We, the undersigned authors of the manuscript entitled

_____________________________________________________________________________________

_____________________________________________________________________________________

warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.

  1. we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
  2. the manuscript does not break the intellectual property rights of any other person.
  3. we have read the submitted version of the manuscript and we are fully responsible for the content.

Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):

  1. ______________________________/_________________________
  2. ______________________________/_________________________
  3. ______________________________/_________________________

N.B.  All the authors must sign this form