Iron Metabolism: A Promising Target for Antibacterial Strategies

Mathieu      Ballouche; Pierre      Cornelis; Christine      Baysse

Abstract

In the fight against pathogenic and opportunistic bacteria, development and spreading of resistance to antibiotics is an increasing public health problem. The available antibacterial treatments are becoming less and less effective, making urgent the discovery of new active molecules. One strategy that has been explored to bypass the bacterial adaptation to drugs is to target the iron metabolism of bacteria, since iron is critical for all bacteria to grow. To date, three major ways have been assessed to exploit weaknesses in the bacterial iron metabolism: the “Trojan Horse strategy” which takes advantages of natural iron-uptake systems to deliver antimicrobial compounds inside the cells; the use of iron-antagonists and iron-chelators in order to reduce iron availability and the inhibition of enzymatic steps of iron metabolism via chemical compounds. This review discusses these antibacterial strategies interfering with several levels of the bacterial iron metabolism, with a special emphasis on recently published and/or patented discoveries.

Keywords: Antibacterial compounds, antibiotics, iron metabolism, siderophore, Trojan Horse strategy, iron chelator, metaloporphyrins, heme uptake