Vol.67 No.2 March 2019
Iron metabolism in infectious diseases -Competition of iron acquisition between the host and bacterial pathogens-
Division of Infection Control and Prevention, Niigata University Medical & Dental Hospital, 1-754 Ichibancho, Asahimachidori, Chuo-ku, Niigata, Japan
Abstract
Iron is essential for both humans and bacteria. Bacteria produce small-molecule siderophores and efficiently acquire iron, and in the presence of an infection, the host and bacteria compete for iron acquisition. The major iron regulator in humans is hepcidin, produced in the liver. Hepcidin controls iron metabolism by inhibiting the expression of the iron transporter, ferroportin. In addition, lipocalin 2, which inhibits siderophores, and Nramp 1, which regulates the iron concentrations in phagosomes, also serve as iron regulators of the host. The iron transport mechanism is considered as a promising target for antibiotics. Cefiderocol (S-649266), with cephalosporin and siderophore structures, can efficiently penetrate the cell outer membrane via the bacterial iron transport system. Application of the iron transport system for drug delivery to treat infectious diseases may be expected with further progress in the understanding of iron metabolism.
Key word
hepcidin, siderophore, lipocalin 2, Nramp 1, cefiderocol
Received
August 28, 2018
Accepted
October 26, 2018
Jpn. J. Chemother. 67 (2): 169-175, 2019
