Siderophore-Antibiotic Conjugates: Applications of the ‘Trojan horse’ Strategy in Anti-Gram-Negative Bacteria Infection
Received date: 2024-07-19
Online published: 2024-08-26
Supported by
National Natural Science Foundation of China(31972850); Open Funding Project of State Key Laboratory of Microbial Metabolism(MMLKF21-09)
The emergence of the "Trojan horse" strategy offers a hopeful remedy for bacterial resistance. Bacterial-derived siderophores exhibit a strong attraction to ferric ion. To create siderophore-antibiotic conjugates, antibiotics are mixed with siderophores. Antibiotics can be directly introduced into bacteria through the bacterial iron transport mechanism to exert their impact and this strategy has demonstrated efficacy in clinical trials. Conjugates of siderophores and antibiotics exhibit potent antibacterial properties against Gram-negative pathogens, which are characterized by intricate cell wall configurations and bacterial external membranes. These conjugates facilitate the movement of antibiotics across membranes linked to them via the bacterial iron transport system, circumventing the permeability hurdles and antibiotic deactivation mechanisms typical of Gram-negative bacteria, and overcoming bacterial resistance. Intriguingly, this strategy also proves successful in combating certain Gram-negative infections using antibiotics targeting infections induced by Gram-positive bacteria. The review delves into recent advancements in treating Gram-negative bacteria using siderophore-antibiotic conjugates and proposes potential future directions for the "Trojan horse" strategy.
Chang Liu , Wengui Wang , Shoufeng Wang . Siderophore-Antibiotic Conjugates: Applications of the ‘Trojan horse’ Strategy in Anti-Gram-Negative Bacteria Infection[J]. Acta Chimica Sinica, 2024 , 82(10) : 1086 -1108 . DOI: 10.6023/A24070222
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