<b>Drug screening to identify compounds to kill </b><b>Burkholderia pseudomallei</b><b> through Hcp protein</b>.zip

Burkholderia pseudomallei exhibits inherent resistance to multiple antibiotics and is prone to developing drug resistance in later stages, leading to a scarcity of effective antibiotics. There is an urgent need to discover effective antibiotics. The type VI secretion system plays a crucial role in the antibiotic resistance and pathogenicity of B. pseudomallei, with Hcp being the major structural protein in this system. Herein, we identify a compound, Netilmicin Sulfate, that binds to Hcp protein and demonstrates optimal bactericidal activity against B. pseudomallei. Netilmicin Sulfate can eradicate B. pseudomallei both in vitro and in vivo, and when combined with Ceftazidime, it exhibits a synergistic effect, enhancing protection of host cells and reducing the required dosage. Molecular docking and molecular dynamics simulations further explore the structure and molecular properties of the Netilmicin Sulfate-Hcp complex. We describe Netilmicin Sulfate as an antibiotic that kills B. pseudomallei throughdisrupting the functional structure of HCP protein. Our findings also provide a potential approach for future antibiotic screening.