ZntR is a critical regulator for zinc homeostasis and involved in pathogenicity in .

Zinc (Zn) is essential for all bacteria, but excessive Zn levels are toxic. Bacteria maintain zinc homeostasis through regulators, such as Zur, AdcR, and ZntR. is a significant pathogen causing acute serositis in ducks and other birds. In this study, we identified a homolog of ZntR, a regulator for zinc homeostasis, and demonstrated its contribution to the pathogenicity of . Deletion of makes the bacteria hypersensitive to excess Zn but not to other metals like manganese (Mn), copper (Cu), cobalt (Co), and nickel (Ni). Deletion of also leads to intracellular zinc accumulation but not of other metals. Additionally, compared to the wild type, the deletion of increases resistance to oxidants hydrogen peroxide (HO) and sodium hypochlorite (NaOCl), respectively. The deletion of causes significant changes in transcriptional and protein expression levels, revealing 35 genes with potential zinc metabolism functions. Among them, , which is inhibited by ZntR, is required for zinc transport and resistance to oxidative stress. Finally, deletion of leads to attenuation of colonization in ducklings. In summary, ZntR is a crucial regulator for zinc homeostasis and contributes to the pathogenicity of .IMPORTANCEZinc homeostasis plays a critical role in the environmental adaptability of bacteria. is a significant pathogen in poultry with the potential to encounter zinc-deficient or zinc-excess environment. The mechanism of zinc homeostasis in this bacterium remains largely unexplored. In this study, we showed that the transcriptional regulator ZntR of is critical for zinc homeostasis by altering the transcription and expression of a number of genes. Importantly, ZntR inhibits the transcription of zinc transporter ZupT and contributes to colonization in . The results are significant for understanding zinc homeostasis and the pathogenic mechanisms in .