Naringenin targets FimZ to regulate type I fimbriae and reduce the virulence of Salmonella

<i>Salmonella</i> infection severely affects the healthy development of livestock and poultry, as well as food safety and public health. The critical role of type I fimbriae (TIFs) in promoting <i>Salmonella</i> pathogenicity makes them important targets for exploring inhibitors of <i>Salmonella</i> infection. In this study, we found that naringenin (Nar) inhibited the invasion of <i>Salmonella</i> into HeLa cells but did not affect bacterial motility. Nar reduced the transcription levels of the TIF structural proteins FimA and FimH and the chaperone proteins FimC and FimD, as determined via RT-qPCR. Molecular docking and surface plasmon resonance (SPR) assays confirmed that Nar was bound to FimZ, which directly regulates the expression of TIF, resulting in a reduction in TIF formation accompanied by a decrease in biofilm formation and bacterial adhesion to cells and alleviation of the inflammatory response. <i>In vivo</i>, Nar prolonged the survival of mice infected with <i>Salmonella</i>, improved the survival rate, reduced the inflammation level and bacterial load, and significantly alleviated histopathological damage. These results provide alternative strategies and promising lead compounds for controlling <i>Salmonella</i> infection.