Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli

摘要

Novel antibacterial agents are urgently needed to address the infections caused by multi-drug resistantbacteria. Urinary tract infections are common infectious diseases in clinical. Most of these infections arecaused 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 thepresent study, two small molecules potentially targeting PPK1 were discovered through virtual screeningand biological assays. The in vitro and in vivo results suggested that the interaction of these compoundswith PPK1 can disrupt biofilm formation of uropathogenic E. coli and reduce invasive ability and resistanceto oxidative stress of this strain. Moreover, the compounds exhibit good antibacterial bacterial activity inthe mice with urinary tract infection. Taken together, our findings could provide a new chemotype for thedevelopment of antibacterials targeting PPK1.