Abstract
AbstractHigh incidences of urinary tract infection (UTI) of aminoglycosides-resistant E.coli causes a severe burden for public health. A new therapeutic strategy to ease this crisis is to repurpose non-antibacterial compounds to increase aminoglycosides sensibility against multidrug resistant E.coli pathogens. Based on high throughput screening technology, we profile the antimicrobial activity of tavaborole, a first antifungal benzoxaborole drug for onychomycosis treatment, and investigate the synergistic interaction between tavaborole and aminoglycosides, especially tobramycin and amikacin. Most importantly, by resistance accumulation assay, we found that, tavaborole not only slowed resistance occurrence of aminoglycosides, but also reduced invasiveness of E.coli in combination with tobramycin. Mechanistic studies preliminary explored that tavaborole and aminoglycosides lead to mistranslation, but would be still necessary to investigate more details for further research. In addition, tavaborole exhibited low systematic toxicity in vitro and in vivo, and enhanced aminoglycoside bactericidal activity in mice peritonitis model. Collectively, these results suggest the potential of tavaborole as a novel aminoglycosides adjuvant to tackle the clinically relevant drug resistant E. coli and encourages us to discover more benzoxaborole analogues for circumvention of recalcitrant infections.
Funder
Graduate Student Independent Exploration Innovation Fund of the Central South University
Natural Science Foundation of Hunan Province
National Natural Science Foundation of China
Key Research and Development Program of Hunan Province of China
Publisher
Springer Science and Business Media LLC
Subject
Applied Microbiology and Biotechnology,Biophysics
Cited by
6 articles.
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