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

Allegra T. Aron, Marie Heffern, Zachery R. Lonergan, Mark N. Vander Wal, Brian R. Blank, Benjamin Spangler, Yaofang Zhang, Hyo Min Park, Andreas Stahl, Adam R. Renslo, Eric P. Skaar, Christopher J. Chang

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 Fe2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe2+ 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.

Original languageEnglish (US)
Pages (from-to)12669-12674
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number48
DOIs
StatePublished - Nov 28 2017

Keywords

  • Infectious disease
  • Labile iron
  • Luciferin
  • Metal homeostasis
  • Molecular imaging

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection'. Together they form a unique fingerprint.

  • Cite this

    Aron, A. T., Heffern, M., Lonergan, Z. R., Vander Wal, M. N., Blank, B. R., Spangler, B., Zhang, Y., Park, H. M., Stahl, A., Renslo, A. R., Skaar, E. P., & Chang, C. J. (2017). In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection. Proceedings of the National Academy of Sciences of the United States of America, 114(48), 12669-12674. https://doi.org/10.1073/pnas.1708747114