Division of Applied Life Science (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Korea.
Molecular Mechanisms of Antibiotics, Division of Life Science, Department of Bio & Medical Big Data (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Korea.
Int J Mol Sci. 2021 May 31;22(11):5936. doi: 10.3390/ijms22115936.
is the one of the most feared bacterial respiratory pathogens in the world. Unfortunately, there are many problems with the current therapies available. These problems include misdiagnoses, high drug resistance, poor long-term treatment outcomes, and high costs. Until now, there have only been a few new compounds or drug formulations which are active against and these are present in preclinical and clinical development only. With that in mind, new and more powerful anti- medicines need to be discovered and developed. In this study, we conducted an in vitro-dual screen against rough (R) and smooth (S) variants using a Pandemic Response Box and identified epetraborole as a new effective candidate for therapy. For further validation, epetraborole showed significant activity against the growth of the wild-type strain, three subspecies, drug-resistant strains and clinical isolates in vitro, while also inhibiting the growth of that reside in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of epetraborole in the zebrafish infection model was greater than that of tigecycline. Thus, we concluded that epetraborole is a potential anti- candidate in the drug search.
是世界上最令人恐惧的细菌性呼吸道病原体之一。不幸的是，目前可用的治疗方法存在许多问题。这些问题包括误诊、高耐药性、长期治疗效果不佳和成本高。到目前为止，只有少数几种新的化合物或药物制剂对 有效，而这些药物制剂仅处于临床前和临床开发阶段。考虑到这一点，需要发现和开发新的、更强大的抗 药物。在这项研究中，我们使用大流行应对盒对 粗糙 (R) 和光滑 (S) 变体进行了体外双重筛选，发现埃皮特罗博雷是一种治疗 的新有效候选药物。为了进一步验证，埃皮特罗博雷在体外显示出对野生型菌株、三个亚种、耐药菌株和临床分离株生长的显著活性，同时抑制巨噬细胞中 的生长而没有细胞毒性。此外，埃皮特罗博雷在斑马鱼感染模型中的体内疗效优于替加环素。因此，我们得出结论，埃皮特罗博雷是 药物搜索中的一种潜在的抗 候选药物。
