An iron-chelating sulfonamide identified from -based screening for antipathogenic discovery.

We exploited bacterial infection assays using the fruit fly to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3--sulfonylpiperidine derivative () protects from the acute infections caused by bacterial pathogens including . did not inhibit the growth of in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in infections and unique transcriptome profile. Taken together, these results delineate a -based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.