Journal
ADVANCED SCIENCE
Volume 7, Issue 17, Pages -Publisher
WILEY
DOI: 10.1002/advs.202001374
Keywords
antibiotics; combination therapy; drug repurposing; macromolecules; reversal of antibiotic resistance phenotype
Categories
Funding
- Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore) [SC 19/08-101002]
- IBM Almaden Research Center
- National Natural Science Foundation of China [81803481, 81830103, 31900982]
- Fundamental Research Funds for the Central Universities of China [20ykpy123, 19ykpy142]
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In order to mitigate antibiotic resistance, a new strategy to increase antibiotic potency and reverse drug resistance is needed. Herein, the translocation mechanism of an antimicrobial guanidinium-functionalized polycarbonate is leveraged in combination with traditional antibiotics to afford a potent treatment for drug-resistant bacteria. Particularly, this polymer-antibiotic combination approach reverses rifampicin resistance phenotype inAcinetobacter baumanniidemonstrating a 2.5 x 10(5)-fold reduction in minimum inhibitory concentration (MIC) and a 4096-fold reduction in minimum bactericidal concentration (MBC). This approach also enables the repurposing of auranofin as an antibiotic against multidrug-resistant (MDR) Gram-negative bacteria with a 512-fold MIC and 128-fold MBC reduction, respectively. Finally, the in vivo efficacy of polymer-rifampicin combination is demonstrated in a MDR bacteremia mouse model. This combination approach lays foundational ground rules for a new class of antibiotic adjuvants capable of reversing drug resistance phenotype and repurposing drugs against MDR Gram-negative bacteria.
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