Iron Uptake Systems: Chemical Tools for Advancing Infectious Disease Treatment and Diagnosis

Microorganisms require iron acquisition, particularly in the form of Fe3+ ions from the external environment, for survival. Siderophores are low-molecular-weight compounds secreted by microorganisms that chelate Fe3+ ions and facilitate their transport into cells. This process forms an Fe3+ uptake system in conjunction with specific transporters, enabling microorganisms to meet their iron requirements. A promising strategy involves utilizing the Fe3+ transport mechanism to deliver siderophore-cargo conjugates into microbial cells, thereby enabling the treatment and diagnosis of infectious diseases, including those caused by drug-resistant bacteria. In this perspective, we systematically evaluate each type of siderophore-antibiotic/fluorophore conjugate and its associated therapeutic and diagnostic outcomes. Through this perspective, we aim to further develop the iron uptake strategy as a means to address the increasingly severe global public health challenge of antimicrobial resistance and to achieve rapid and ultrasensitive diagnosis of infections, encompassing but not limited to bacterial and fungal infections.