1. Academic Validation
  2. Drug synergy discovery of tavaborole and aminoglycosides against Escherichia coli using high throughput screening

Drug synergy discovery of tavaborole and aminoglycosides against Escherichia coli using high throughput screening

  • AMB Express. 2022 Dec 1;12(1):151. doi: 10.1186/s13568-022-01488-6.
Shasha Liu 1 Pengfei She 1 Zehao Li 1 Yimin Li 1 Linhui Li 1 Yifan Yang 1 Linying Zhou 2 Yong Wu 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.
  • 2 Department of Laboratory Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, Hunan, China.
  • 3 Department of Laboratory Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, Hunan, China. wuyong_zn@csu.edu.cn.
Abstract

High 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.

Keywords

Benzoxaborole; Drug repurposing; Drug resistance; Microbial proteomics; Uropathogenic Escherichia col.

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