Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.

中文翻译：

---

FDA批准的鼠疫耶尔森氏菌新药库的筛选

鼠疫耶尔森氏菌是革兰氏阴性病原体，可引起鼠疫，这是一种毁灭性疾病，在全球范围内造成数百万人死亡。尽管可以通过推荐的抗生素有效地治疗鼠疫，但是抗生素治疗的开始时间至关重要，因为如果症状发作后延迟治疗超过24小时，则观察到很高的死亡率。为了克服抗生素抗性菌株的出现，我们尝试对食品药品监督管理局（FDA）批准的药物进行系统的筛选，以鉴定可能具有对鼠疫耶尔森氏菌具有抗菌活性的替代化合物。。在这里，我们描述了一种药物再利用的方法，该方法导致了抗癌药硫酸博来霉素和链霉素的两种类抗生素活性的鉴定，这些活性具有设计新型抗瘟治疗方法的潜力。进一步探讨了这两种药物的抑制特性，以及它们在影响对强力霉素和环丙沙星（推荐用于鼠疫治疗的抗生素）的鼠疫耶尔森氏菌菌株的生长中的效率。