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.

氨基糖苷类耐药大肠杆菌尿路感染（UTI）的高发给公众健康带来了严重负担。缓解这一危机的新治疗策略是重新利用非抗菌化合物，以提高氨基糖苷类药物对多重耐药大肠杆菌病原体的敏感性。基于高通量筛选技术，我们分析了首个用于治疗甲癣的抗真菌苯并沙硼罗药物tavaborole的抗菌活性，并研究了tavaborole与氨基糖苷类药物，特别是妥布霉素和阿米卡星之间的协同相互作用。最重要的是，通过耐药累积测定，我们发现，他伐硼罗不仅减缓了氨基糖苷类耐药的发生，而且与妥布霉素合用还降低了大肠杆菌的侵袭性。机制研究初步探讨了他伐硼罗和氨基糖苷类药物会导致误译，但仍需要调查更多细节以供进一步研究。此外，tavaborole 在体外和体内表现出较低的系统毒性，并在小鼠腹膜炎模型中增强氨基糖苷类杀菌活性。总的来说，这些结果表明他伐硼罗作为一种新型氨基糖苷类佐剂来应对临床相关的耐药大肠杆菌的潜力，并鼓励我们发现更多的苯并恶硼罗类似物来规避顽固性感染。