Siderophores in Iron Metabolism: From Mechanism to Therapy Potential.
Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by secreting siderophores, small ferric iron-binding molecules. In response, host immune cells secrete lipocalin 2 (also known as siderocalin), a siderophore-binding protein, to prevent bacterial reuptake of iron-loaded siderophores. To counter this threat, some bacteria can produce lipocalin 2-resistant siderophores. This review discusses the recently described molecular mechanisms of siderophore iron trafficking between host and bacteria, highlighting the therapeutic potential of exploiting pathogen siderophore machinery for the treatment of antibiotic-resistant bacterial infections. Because the latter reflect a persistent problem in hospital settings, siderophore-targeting or siderophore-based compounds represent a promising avenue to combat such infections.
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7633, USA.
Briana R
BR
Wilson
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7633, USA.
Alexander R
AR
Bogdan
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7633, USA.
Masaki
M
Miyazawa
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7633, USA.
Kazunori
K
Hashimoto
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7633, USA. Electronic address: ytsuji@ncsu.edu.
Yoshiaki
Y
Tsuji
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D055808:Drug Discovery; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000276:immunology / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000276:immunology / Q000378:metabolism*; D017262:Siderophores / Q000276:immunology / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000071068:Lipocalin-2; D017262:Siderophores; D007501:Iron
Lcn2; hypoxia; iron; mitophagy; siderocalin; siderophore