Heavy-Metal Trojan Horse: Enterobactin-Directed Delivery of Platinum(IV) Prodrugs to Escherichia coli.

ABSTRACT: The global crisis of untreatable microbial infections necessitates the design of new antibiotics. Drug repurposing is a promising strategy for expanding the antibiotic repertoire. In this study, we repurpose the clinically approved anticancer agent cisplatin into a targeted antibiotic by conjugating its Pt(IV) prodrug to enterobactin (Ent), a triscatecholate siderophore employed by Enterobacteriaceae for iron (Fe) acquisition. The l-Ent-Pt(IV) conjugate (l-EP) exhibits antibacterial activity against Escherichia coli K12 and the uropathogenic isolate E. coli CFT073. Similar to cisplatin, l-EP causes a filamentous morphology in E. coli and initiates lysis in lysogenic bacteria. Studies with E. coli mutants defective in Ent transport proteins show that Ent mediates

SUBMITTER: Guo C 

PROVIDER: S-EPMC9347114 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature