Trojan Horses: Conjugating Siderophores and Antibiotics—A New Approach to Treating Pseudomonas aeruginosa Infection

Pseudomonas aeruginosa is a common Gram-negative bacterium in hospital infections and one of the main pathogens causing opportunistic infections in humans. In recent years, the drug resistance of P. aeruginosa has become increasingly severe. Therefore, it is urgent to explore new targets for antibacterial therapy. In P. aeruginosa, iron is an essential element not only for cell growth but also for successful infection. Two siderophores are produced by P. aeruginosa: pyoverdine and pyochelin. They help P. aeruginosa to obtain iron and play an important role in interspecific competition, anti-oxidative stress, and virulence. Furthermore, siderophores have been used to design “Trojan horse” antibiotics. These antibiotic–siderophore conjugates enter the cytoplasm of P. aeruginosa via siderophore uptake systems for pyoverdine and pyochelin, releasing antibacterial substances and exerting corresponding effects against P. aeruginosa. This review discusses the synthesis, secretion, and uptake of siderophores in P. aeruginosa as well as the role of the “Trojan horse” strategy in treating P. aeruginosa infections.