New insights into the antimicrobial action and protective therapeutic effect of tirapazamine towards Escherichia coli-infected mice

•The tirapazamine (TPZ) inhibits Escherichia coli proliferation in vitro and in vivo.•The resistance reversal activity of TPZ was achieved by regulating genes related to drug resistance and biofilm formation in E. coli.•Proteomics analysis showed that the antibacterial activity of TPZ toward E. coli may be achieved by damaging bacterial DNA.•TPZ improved the survival rate of E. coli infected mice, the protective therapeutic effect of TPZ on mice may also be related to the modulation of gut microbiota.