The power of DNA-encoded chemical libraries in the battle against drug-resistant bacteria

Drug-resistant bacteria are increasingly posing an imminent existential threat, as many bacteria have developed resistance mechanisms that render most antibiotics ineffective. In the meantime, the number of newly approved antibiotics or new clinical antibacterial drug candidates is sharply declining. A key challenge is finding effective pharmacophores that can penetrate and accumulate inside bacterial cells. DNA-encoded chemical libraries (DECLs) play vital roles in accelerating hit identification and screening against various bacterial protein targets. In this review, we highlight the pivotal role of DECLs in accelerating the identification of new pharmacophores and hit compounds against drug-resistant bacteria. This review focuses on the protein targets, where DECLs have directly contributed to the rapid identification of new inhibitors. In addition, this review explores the methods used to screen DECLs against various bacterial targets and discusses the current outlook and perspectives on the role of DECLs in tackling antimicrobial resistance.