Breaking a pathogen's iron will: Inhibiting siderophore production as an antimicrobial strategy

•Antibiotic resistance is a growing international health concern.•Iron nutritional immunity is a target for antimicrobial drug design.•NRPS, PKS and NIS siderophore production is described.•Inhibitors designed rationally are documented.•Inhibitors identified by high throughput screening are reported.

The rise of antibiotic resistance is a growing public health crisis. Novel antimicrobials are sought, preferably developing nontraditional chemical scaffolds that do not inhibit standard targets such as cell wall synthesis or the ribosome. Iron scavenging has been proposed as a viable target, because bacterial and fungal pathogens must overcome the nutritional immunity of the host to be virulent. This review highlights the recent work toward exploiting the biosynthetic enzymes of siderophore production for the design of next generation antimicrobials.