Natural sideromycins and siderophore-conjugated natural products as inspiration for novel antimicrobial agents

Multidrug-resistant Gram-negative pathogens pose a significant challenge to clinical anti-infective therapy. A promising strategy involves conjugating antibiotics to siderophore molecules, resulting in siderophore-antibiotic conjugates (SACs). These SACs deliver antibiotics directly into cells, bypassing the outer membrane permeability barrier. The first SAC, cefiderocol, has sparked interest among researchers and pharmaceutical companies. Research on siderophore-natural product conjugates as novel antimicrobial agents since 2010 is summarized, with challenges and prospects for future development.