Please use this identifier to cite or link to this item: https://doi.org/10.1002/advs.202001374
Title: A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics
Authors: Ding, Xin
Yang, Chuan 
Moreira, Wilfried 
Yuan, Peiyan
Periaswamy, Balamurugan
de Sessions, Paola Florez
Zhao, Huimin
Tan, Jeremy
Lee, Ashlynn
Ong, Kai Xun
Park, Nathaniel
Liang, Zhen Chang
Hedrick, James L
Yang, Yi Yan
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Chemistry
Science & Technology - Other Topics
Materials Science
antibiotics
combination therapy
drug repurposing
macromolecules
reversal of antibiotic resistance phenotype
BROAD-SPECTRUM
ACINETOBACTER-BAUMANNII
AMINOGLYCOSIDE-RESISTANCE
MOLECULAR EPIDEMIOLOGY
COMBINATION THERAPY
DELIVERY-SYSTEMS
POLYCARBONATES
COLISTIN
PROTEIN
ANTIBACTERIAL
Issue Date: 21-Jul-2020
Publisher: WILEY
Citation: Ding, Xin, Yang, Chuan, Moreira, Wilfried, Yuan, Peiyan, Periaswamy, Balamurugan, de Sessions, Paola Florez, Zhao, Huimin, Tan, Jeremy, Lee, Ashlynn, Ong, Kai Xun, Park, Nathaniel, Liang, Zhen Chang, Hedrick, James L, Yang, Yi Yan (2020-07-21). A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics. ADVANCED SCIENCE 7 (17). ScholarBank@NUS Repository. https://doi.org/10.1002/advs.202001374
Abstract: 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 in Acinetobacter baumannii demonstrating a 2.5 × 105-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.
Source Title: ADVANCED SCIENCE
URI: https://scholarbank.nus.edu.sg/handle/10635/225216
ISSN: 21983844
DOI: 10.1002/advs.202001374
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