Amphiphilic nebramine-based hybrids Rescue legacy antibiotics from intrinsic resistance in multidrug-resistant Gram-negative bacilli.
作者： Xuan Yang , Derek Ammeter , Temilolu Idowu , Ronald Domalaon , Marc Brizuela
DOI: 10.1016/J.EJMECH.2019.05.003
关键词: Rifampicin 、 Antibiotics 、 Ciprofloxacin 、 Adjuvant 、 Rifamycin 、 Microbiology 、 Chemistry 、 Aminoglycoside 、 Multiple drug resistance 、 Tobramycin
摘要: Abstract The inability to discover novel class of antibacterial agents, especially against Gram-negative bacteria (GNB), compel us consider a broader non-conventional approach treat infections caused by multidrug-resistant (MDR) bacteria. One such is the use adjuvants capable revitalizing activity current existing antibiotics from resistant pathogens. Recently, our group reported series tobramycin (TOB)-based hybrid that were able potentiate multiple classes legacy various MDR GNB. Herein, we report modification TOB-based replacing TOB domain pseudo-disaccharide nebramine (NEB) through selective cleavage α- d -glucopyranosyl linkage TOB. Potent synergism was found for combinations NEB-based with including fluoroquinolones (moxifloxacin and ciprofloxacin), tetracyclines (minocycline), or rifamycin (rifampicin) both wild-type P. aeruginosa clinical isolates. We also demonstrated combination optimized NEB-CIP 1b rifampicin protects Galleria mellonella larvae lethal effects extensively drug-resistant (XDR) P. aeruginosa. Mechanistic evaluation revealed hybrids affect outer- inner membranes PAO1. This study describes an optimize aminoglycoside-based yield lead adjuvant candidates are resuscitate partner
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