Bacterial iron uptake: a promising solution against multidrug resistant bacteria

The emergence of nosocomial diseases driven by multidrug resistant bacteria is a major issue for our healthcare system. Mechanisms underlying multidrug resistance in these bacteria can be linked to the decreased permeability of bacterial membranes towards antibiotics, either by structural modifications inducing reduced passive diffusion, or by decreasing active uptake systems. Micro-organisms need iron which is present in low quantity in biological media for their development and absorb it via specific receptors or uptake mechanisms. Bacteria synthesize low-weight molecules called siderophores that strongly bind extracellular ferric iron and are recognized by membrane receptors and transported into the bacterial cytoplasm. In this paper, we propose to review the various siderophores and uptake complexes existing in Gramnegative bacteria, the naturally occurring molecules using a Trojan horse strategy via bacterial iron uptake systems to enter and kill bacteria and to make a state-of-the-art of the synthetic molecules so far developed using siderophore-like (ironchelating) agents coupled with antibiotic molecules.