Overcoming Acquired and Native Macrolide Resistance with Bicarbonate
| Autor: | Andrew G. McArthur, Craig R. MacNair, Hiu-Ki R Tran, Lindsey A. Carfrae, Eric D. Brown, Sara S. El Zahed, Michael J. Ellis, Maya A. Farha |
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| Rok vydání: | 2020 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine medicine.drug_class Bicarbonate 030106 microbiology Antibiotics Drug uptake Microbiology Macrolide Antibiotics Bacterial protein Mice 03 medical and health sciences chemistry.chemical_compound Microbial resistance Drug Resistance Bacterial medicine Animals business.industry Anti-Bacterial Agents 3. Good health Bicarbonates 030104 developmental biology Infectious Diseases chemistry Mechanism of action Macrolide resistance Macrolides medicine.symptom business |
| Zdroj: | ACS Infectious Diseases. 6:2709-2718 |
| ISSN: | 2373-8227 |
| DOI: | 10.1021/acsinfecdis.0c00340 |
| Popis: | The growing challenge of microbial resistance emphasizes the importance of new antibiotics or reviving strategies for the use of old ones. Macrolide antibiotics are potent bacterial protein synthesis inhibitors with a formidable capacity to treat life-threatening bacterial infections; however, acquired and intrinsic resistance limits their clinical application. In the work presented here, we reveal that bicarbonate is a potent enhancer of the activity of macrolide antibiotics that overcomes both acquired and intrinsic resistance mechanisms. With a focus on azithromycin, a highly prescribed macrolide antibiotic, and using clinically relevant pathogens, we show that physiological concentrations of bicarbonate overcome drug resistance by increasing the intracellular concentration of azithromycin. We demonstrate the potential of bicarbonate as a formulation additive for topical use of azithromycin in treating a murine wound infection caused by |
| Databáze: | OpenAIRE |
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