Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli
Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli
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针对尿路致病性大肠杆菌的潜在 PPK1 抑制剂的发现和抗菌研究
DOI：
10.1080/14756366.2020.1766453
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Sun, Ning
中科院分区：
文献类型：
--
作者：
Peng, Liang;Zeng, Liting;Sun, Ning
摘要针对多重耐药菌引起的感染，迫切需要新型抗菌药物。尿路感染是临床常见的感染性疾病。这些感染大多数是由耐药性尿路致病性大肠杆菌引起的。PPK1是细菌运动、生物膜形成、群体感应和致病性大肠杆菌表达中的毒力因子的必需激酶。杆菌在本研究中，通过虚拟筛选和生物测定发现了两个潜在靶向PPK1的小分子。体外和体内实验结果表明，这些化合物与PPK1的相互作用可以破坏尿路致病性大肠杆菌生物膜的形成。大肠杆菌的侵袭能力和抗氧化应激能力。此外，这些化合物在尿路感染的小鼠中显示出良好的抗菌活性。总之，我们的研究结果可以为开发针对PPK1的抗菌药物提供新的化学型。图形摘要
Abstract Novel antibacterial agents are urgently needed to address the infections caused by multi-drug resistant bacteria. Urinary tract infections are common infectious diseases in clinical. Most of these infections are caused by drug-resistant uropathogenic Escherichia coli. PPK1 is an essential kinase for bacterial motility, biofilm formation, quorum sensing, and virulence factors in the expression of uropathogenic E. coli. In the present study, two small molecules potentially targeting PPK1 were discovered through virtual screening and biological assays. The in vitro and in vivo results suggested that the interaction of these compounds with PPK1 can disrupt biofilm formation of uropathogenic E. coli and reduce invasive ability and resistance to oxidative stress of this strain. Moreover, the compounds exhibit good antibacterial bacterial activity in the mice with urinary tract infection. Taken together, our findings could provide a new chemotype for the development of antibacterials targeting PPK1. Graphical Abstract