[Frontiers in Bioscience, Landmark, 25, 673-682, Jan 1, 2020]

Iron should be restricted in acute infection

Cassidy R Scott1, Bruce E Holbein2, Christian D Lehmann3-5

1Department of Psychology and Neuroscience, Dalhousie University, Halifax, Canada, 2Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada, 3Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada, 4Department of Pharmacology, Dalhousie University, Halifax, Canada, 5Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Iron restriction
    3.1. Learning from microbes
    3.2. Restricting iron with synthetic iron chelators
    3.3. Other bacterial strategies for iron acquisition as drug target for new antibiotics
    3.4. Siderophores as gates for antibiotics
    3.5. Iron chelation overcomes antibiotic resistances
4. Limitations of iron witholding
5. Conclusion
6. References

1. ABSTRACT

The trace element iron plays important roles in biological systems. Vital functions of both host organisms and pathogens require iron. During infection, the innate immune system reduces iron availability for invading organisms. Pathogens acquire iron through different mechanisms, primarily through the secretion of high-affinity iron chelating compounds known as siderophores. Bacterial siderophores have been used clinically for iron chelation, however synthetic iron chelators are superior for treating infection because - in contrast to siderophore-bound iron - bacteria are not able to utilize iron bound to those molecules. Additionally, utilizing siderophores-dependent iron uptake in a “trojan horse” manner represents a potential option to carry antibiotics into bacterial cells. Recently, synthetic iron chelators have been shown to enhance antibiotic effectiveness and overcome antibiotic resistance. This has implications for the treatment of infections through combination therapy of iron chelators and antibiotics.

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Key Words: Review, Iron, Chelation, Acute Infection, Antibiotics, Metabolism, Review

Send correspondence to: Dr. Christian Lehmann, Dept. of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Sir Charles Tupper Medical Building, Room 6H-1, 5850 College Street, Halifax, NS B3H1X5, Canada, Tel.: 902-494-1287, E-mail: chlehmann@dal.ca