Abstract
The spread of multidrug-resistant Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA), has shortened the useful life of anti-staphylococcal drugs enormously. Two approaches can be followed to address this problem: screening various sources for new leads for antibiotics or finding ways to disable the resistance mechanisms to existing antibiotics. Plants are resistant to most microorganisms, but despite extensive efforts to identify metabolites that are responsible for this resistance, no substantial progress has been made. Plants possibly use multiple strategies to deal with microorganisms that evolved over time. For this reason, we searched for plants that could potentiate the effects of known antibiotics. From 29 plant species tested, Cytisus striatus clearly showed such an activity and an NMR-based metabolomics study allowed the identification of compounds from the plant extracts that could act as antibiotic adjuvants. Isoflavonoids were found to potentiate the effect of ciprofloxacin and erythromycin against MRSA strains. For the structure-activity relationship (SAR), 22 isoflavonoids were assessed as antibiotic adjuvants. This study reveals a clear synergy between isoflavonoids and the tested antibiotics, showing their great potential for applications in the clinical therapy of infections with antibiotic-resistant microorganisms such as MRSA.
Highlights
The worldwide spread of multidrug-resistant (MDR) bacteria is increasingly attracting the attention of global surveillance authorities and media, and is undoubtedly rated as a major health threat in the 21st century
Testing different bacterial strains should show whether the mode of action of the plant extract and its interaction with the antibiotic depends on the resistance profile of the strains
It is known that plants can produce inhibitors as a protection against multidrug-resistant pathogens, thereby ensuring the efficient delivery of antimicrobial compounds
Summary
The worldwide spread of multidrug-resistant (MDR) bacteria is increasingly attracting the attention of global surveillance authorities and media, and is undoubtedly rated as a major health threat in the 21st century. The goal of this study, is to test whether it is possible to take advantage of a plant’s powerful defense system, presumably based on complex synergistic interactions, to potentiate the activity of known antibiotics. Such a complex biological question is perfectly suited to a systems biology approach since a reductionist approach such as the conventional bioassay-guided fractionation cannot reveal interactions between compounds, such as synergy. The step was to isolate the compounds responsible for these signals by NMR-based metabolomics guided fractionation, identify them and test various combinations for a synergistic antimicrobial potentiating activity on MRSA strains
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