High-throughput screening unveils AMG 837 and RORγt 13 as the potent Brucella inhibitor by targeting BacA

Brucellosis poses a major threat to the global animal husbandry, yet effective prevention and control measures remain elusive. Through High-Throughput Screening techniques, two potential anti-Brucella compounds are identified from a library comprising FDA-approved and known biological activity in this study. We unveil AMG 837 calcium hydrate and RORγt inverse antigen 13 can strongly bind with BacA, which mutants lacking BacA greatly reduce the survival rate of Brucella in macrophages. AMG 837 calcium hydrate and RORγt inverse antigen 13 as the potent inhibitor of Brucella both in vitro and in cells, which can effectively eliminate bacteria that infect into cells at a concentration of only 16 μg/mL. These results indicate the promising potential of AMG 837 calcium hydrate and RORγt inverse antigen 13 as the repurposed therapeutic agent for brucellosis. Additionally, they provide valuable insights into the antibacterial mechanisms underlying effectiveness.