Golden Martina M, Heppe Amelia C, Zaremba Cassandra L, Wuest William M
Department of Chemistry, Emory University Atlanta GA 30322 USA
Department of Chemistry and Biochemistry, Denison University Granville OH 43023 USA
RSC Chem Biol. 2024 Sep 24;5(11):1083-96. doi: 10.1039/d4cb00175c.
It is estimated that by 2050, bacterial infections will cause 1.8 million more deaths than cancer annually, and the current lack of antibiotic drug discovery is only exacerbating the crisis. Two pathogens in particular, Gram-negative bacteria and , are of grave concern because of their heightened multi-drug resistance due to a dense, impermeable outer membrane. However, targeting specific cellular processes may prove successful in overcoming bacterial resistance. This review will concentrate on a novel approach to combatting pathogenicity by disarming bacteria through the disruption of metal homeostasis to reduce virulence and enhance antibiotic uptake. The varying levels of success in bringing metallophores to clinical trials, with currently only one FDA-approved siderophore antibiotic to date, will also be detailed.
据估计，到2050年，细菌感染每年将比癌症多导致180万人死亡，而目前抗生素药物研发的匮乏只会加剧这一危机。特别是两种病原体，革兰氏阴性菌和（此处原文缺失一种病原体名称），因其致密、不可渗透的外膜导致多药耐药性增强而备受关注。然而，针对特定细胞过程可能被证明在克服细菌耐药性方面是成功的。本综述将集中探讨一种新的方法，即通过破坏金属稳态来消除细菌的毒性并增强抗生素摄取，从而对抗致病性。还将详细介绍将金属载体推进临床试验所取得的不同程度的成功，目前只有一种铁载体抗生素获得了美国食品药品监督管理局（FDA）的批准。
