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Natural Product BO-1 as an Inner Responsive Molecule Inhibits Antimicrobial-Resistant Staphylococcus aureus via
Chuan-Yun Xiao1, Jiao Huang1, Xiao Liu1
1School of Pharmacy, Fudan University, Shanghai 201203, China.
ACS Infectious Diseases
|July 7, 2023
Summary
A novel compound, BO-1, from Piper betle L. synergizes with antibiotics to combat multidrug-resistant Staphylococcus aureus. This inner responsive molecule (IRM) inhibits efflux activity, restoring antibiotic sensitivity and reducing inflammation in animal models.
Area of Science:
- Microbiology
- Pharmacology
- Natural Products Chemistry
Background:
- Multidrug-resistant Staphylococcus aureus (MRSA) poses a significant global health threat, necessitating novel therapeutic strategies.
- Existing antibiotics are becoming less effective due to bacterial resistance mechanisms, particularly efflux pumps.
- Inner responsive molecules (IRMs) are hypothesized to restore antibiotic sensitivity without inducing further resistance.
Purpose of the Study:
- To identify and characterize IRMs from Piper betle L. that can synergize with antibiotics against MRSA.
- To elucidate the mechanism of action of identified IRMs, focusing on resistance suppression.
- To evaluate the therapeutic potential of IRM-antibiotic combinations in preclinical models.
Main Methods:
- Extraction and isolation of compounds from Piper betle L. using chromatographic techniques.
- In vitro testing of isolated compounds for synergistic antibacterial activity against resistant S. aureus strains.
- Mechanistic studies involving efflux inhibition assays and resistance reversal experiments.
- In vivo efficacy evaluation in animal models of S. aureus infection, assessing bacterial load and inflammatory markers.
Main Results:
- Six benzoate esters (BO-1 to BO-6) were isolated from Piper betle L. extract.
- BO-1 demonstrated significant synergistic activity, potentiating ciprofloxacin's efficacy against multiple resistant S. aureus strains.
- Mechanistic studies confirmed BO-1 acts as an efflux inhibitor, suppressing drug resistance.
- Combination therapy with BO-1 and ciprofloxacin reversed antibiotic resistance and reduced inflammatory markers (IL-6, C-reactive protein) in infected mice.
Conclusions:
- BO-1 is a potent IRM capable of restoring antibiotic sensitivity in multidrug-resistant S. aureus by inhibiting efflux pumps.
- The combination of BO-1 with ciprofloxacin offers a promising strategy to overcome antibiotic resistance and treat S. aureus infections.
- Piper betle L. serves as a valuable source for novel compounds with potential applications in combating antimicrobial resistance.
Keywords:
antibiotic resistanceantibiotic-resistant Staphylococcus aureusbenzoate estersinner responsive moleculesynergistic antibacterialMore Related Videos
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