GaSal-2: A Water-Soluble Antipseudomonal Agent Targeting the Extracellular Hemophore HasAp.

Multidrug-resistant is a critical pathogen that demands new antibiotics. During infection, the extracellular hemophore and its outer membrane receptor are the most dramatically upregulated genes. The Δ strain exhibits significantly reduced growth and virulence. We previously described a gallium salophen complex GaSal that demonstrated antipseudomonal potential by targeting HasAp. Here, we report the development of a water-soluble derivative, GaSal-2, which tightly binds to HasAp, blocks transcriptional activation of the bacterial cell surface signaling cascade, inhibits growth, and effectively disrupts established biofilms. Moreover, GaSal-2 is not toxic to human lung fibroblasts and hepatocytes. It has shown promising antipseudomonal effects in a murine lung infection model.