A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics

Autor: Xin Ding, Chuan Yang, Wilfried Moreira, Peiyan Yuan, Balamurugan Periaswamy, Paola Florez deSessions, Huimin Zhao, Jeremy Tan, Ashlynn Lee, Kai Xun Ong, Nathaniel Park, Zhen Chang Liang, James L. Hedrick, Yi Yan Yang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Advanced Science, Vol 7, Iss 17, Pp n/a-n/a (2020)
Druh dokumentu: article
ISSN: 2198-3844
20200137
DOI: 10.1002/advs.202001374
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje