Research advances of linkers in the design of siderophore-antibiotic conjugates

Abstract:

Escalating resistance of pathogens, especially Gram-negative bacteria, to antibiotics has become a public health problem arousing worldwide concern because of the abuse of antibiotics. The “Trojan Horse” strategy emerges as a promising approach to the development of new antibacterial agents. This strategy improves the antibacterial activity or broadens the antibacterial spectrum of antibiotics by using the siderophore-mediated bacterial iron transport system. In 2019, cefiderocol as the first siderophore-antibiotic conjugate was approved for marketing, which has garnered wide attention of scientists in this field. Currently, researchers mainly focus on siderophores or utilizing antibiotics with different mechanisms and ignoring linkers in the design of agents based on the “Trojan Horse” strategy. This review will summarize the impact of different linkers of conjugates on antibacterial activity, which could provide reference for the development of new antibacterial drugs and combating bacterial resistance.