In vivo bioluminescence imaging of labile iron accumulation in a murine model of infection.

Aron AT, Heffern MC, Lonergan ZR, Vander Wal MN, Blank BR, Spangler B, Zhang Y, Park HM, Stahl A, Renslo AR, Skaar EP, Chang CJ
Proc Natl Acad Sci U S A. 2017 114 (48): 12669-12674

PMID: 29138321 · PMCID: PMC5715752 · DOI:10.1073/pnas.1708747114

Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release d-aminoluciferin for selective reactivity-based detection of Fe with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.

MeSH Terms (25)

2,2'-Dipyridyl Acinetobacter baumannii Acinetobacter Infections Anemia, Iron-Deficiency Animals Cations, Divalent Cation Transport Proteins Disease Models, Animal Ferric Compounds Firefly Luciferin Fluorescent Dyes Gene Expression Regulation Hepcidins Homeostasis Iron Iron Overload Iron Regulatory Protein 1 Iron Regulatory Protein 2 Luminescent Measurements Mice Mice, Transgenic Quaternary Ammonium Compounds Receptors, Transferrin Signal Transduction Transferrin

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