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Iron should be restricted in acute infection
Cassidy R Scott1, Bruce E Holbein2, Christian D Lehmann3
1Department of Psychology and Neuroscience, Dalhousie University, Halifax, Canada.
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.
Insights
Synthetic iron chelators offer a superior approach to treating infections by limiting pathogen iron access. They can also be used with antibiotics to enhance effectiveness and combat resistance.
Area of Science:
- Biochemistry
- Immunology
- Microbiology
Background:
- Iron is essential for both host and pathogen biological functions.
- The innate immune system restricts iron availability during infection.
- Pathogens utilize siderophores for iron acquisition.
Purpose of the Study:
- To explore the therapeutic potential of synthetic iron chelators in combating bacterial infections.
- To investigate the use of synthetic iron chelators as a delivery mechanism for antibiotics.
- To evaluate the efficacy of combination therapy involving iron chelators and antibiotics.
Main Methods:
- Review of existing literature on iron metabolism in host-pathogen interactions.
- Analysis of the mechanisms of action for siderophores and synthetic iron chelators.
- Examination of studies demonstrating the synergistic effects of iron chelators and antibiotics.
Main Results:
- Synthetic iron chelators effectively block bacterial iron uptake, unlike siderophore-bound iron.
- Synthetic chelators can be engineered to act as 'Trojan horses' for antibiotic delivery.
- Combination therapy with synthetic iron chelators enhances antibiotic effectiveness and overcomes resistance.
Conclusions:
- Synthetic iron chelators represent a promising strategy for treating infections.
- Combination therapy of iron chelators and antibiotics offers a novel approach to combatting antibiotic resistance.
- Further research into synthetic iron chelators could revolutionize infection treatment.
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