Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance

The rise of antimicrobial resistance (AMR) necessitates alternative strategies. This study investigates the synergistic effects of cefiderocol (a sideromycin) and metallodrugs (e.g., colloidal bismuth citrate, CBS) against drug-resistant Gram-negative bacteria, specifically *Pseudomonas aeruginosa* and *Burkholderia cepacia*. CBS enhances cefiderocol's efficacy against biofilm formation, suppresses resistance development, and resensitizes resistant strains. In a murine pneumonia model, CBS-cefiderocol co-therapy significantly improved survival and reduced bacterial lung burden. This synergy is partly due to Bi³⁺ competing with Fe³⁺ for binding to cefiderocol, increasing Bi³⁺ uptake and reducing Fe³⁺ levels.

Chenyuan Wang, Yushan Xia, Runming Wang, Jingru Li, Chun-Lung Chan, Richard Yi-Tsun Kao, Patrick H. Toy, Pak-Leung Ho, Hongyan Li, Hongzhe Sun