Metal chelation as an antibacterial strategy for and

• Published in: RSC chemical biology 2024-10, Vol.5 (11), p.183-196
• Main Authors: Golden, Martina M, Heppe, Amelia C, Zaremba, Cassandra L, Wuest, William M
• Format: Article
• ISSN: 2633-0679
• 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 A. baumannii and P. aeruginosa , 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. A. baumannii and P. aeruginosa pose serious concerns due to heighted multi-drug resistance. A novel method to reduce bacterial virulence and enhance the effectiveness of antibiotics may be achieved by disrupting native metal homeostasis.