Sophoraflavanone G Ameliorates Riemerella anatipestifer infection in vivo and in vitro

Riemerella anatipestifer (R. anatipestifer) poses a serious threat to poultry, leading to substantial economic losses to the poultry industry. The escalating prevalence of antibiotic resistance in R. anatipestifer underscores the urgent need for novel therapeutic agents. In this study, we demonstrated that Sophoraflavanone G (SFG), a lavandulylated flavanone derived from Sophora flavescens, exhibits rapid bactericidal activity against R. anatipestifer in vitro and shows a low propensity for inducing drug resistance. Mechanistic studies indicate that SFG binds to phosphatidylglycerol, compromising the structural and functional integrity of the cytoplasmic membrane in R. anatipestifer, which results in the leakage of intracellular contents. Further studies demonstrate that SFG disrupts bacterial proton motive force, promotes the intracellular accumulation of ATP and reactive oxygen species, and inhibits DNA and RNA biosynthesis. In the peritonitis model, SFG treatment significantly reduced the bacterial load in the tissues of infected ducklings and attenuated the tissue damage caused by R. anatipestifer infection. In conclusion, SFG represents a promising antibacterial agent with a low propensity for resistance development, offering potential for combating R. anatipestifer infections.