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.

中文翻译：

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针对尿毒症性大肠杆菌的潜在PPK1抑制剂的发现和抗菌研究。

迫切需要新型抗菌剂来解决由多重耐药细菌引起的感染。尿路感染是临床上常见的传染病。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是尿路致病性大肠杆菌表达中细菌活力，生物膜形成，群体感应和毒力因子的必需激酶。在本研究中，通过虚拟筛选和生物学分析发现了两个潜在的靶向PPK1的小分子。体外和体内结果表明，这些化合物与PPK1的相互作用可以破坏尿毒症性大肠杆菌的生物膜形成，并降低该菌株的侵袭能力和对氧化应激的抵抗力。此外，该化合物在尿路感染的小鼠中表现出良好的抗菌活性。综上所述，我们的发现可以为靶向PPK1的抗菌素的开发提供一种新的化学型。