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Leveraging copper import by yersiniabactin siderophore system for targeted PET imaging of bacteria
Nabil A. Siddiqui, Hailey A. Houson, Nitin S. Kamble, Jose R. Blanco, Robert E. O’Donnell, Daniel J. Hassett, Suzanne E. Lapi, Nalinikanth Kotagiri
Nabil A. Siddiqui, Hailey A. Houson, Nitin S. Kamble, Jose R. Blanco, Robert E. O’Donnell, Daniel J. Hassett, Suzanne E. Lapi, Nalinikanth Kotagiri
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Resource and Technical Advance Infectious disease

Leveraging copper import by yersiniabactin siderophore system for targeted PET imaging of bacteria

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Abstract

There is an emerging need for accurate and rapid identification of bacteria in the human body to achieve diverse biomedical objectives. Copper homeostasis is vital for the survival of bacterial species owing to the roles of the metal as a nutrient, respiratory enzyme cofactor, and a toxin. Here, we report the development of a copper-64–labeled bacterial metal chelator, yersiniabactin, to exploit a highly conserved metal acquisition pathway for noninvasive and selective imaging of bacteria. Compared with traditional techniques used to manufacture probes, our strategy simplifies the process considerably by combining the function of metal attachment and cell recognition to the same molecule. We demonstrate, for the first time to our knowledge, how a copper-64 PET probe can be used to identify specific bacterial populations, monitor antibiotic treatment outcomes, and track bacteria in diverse niches in vivo.

Authors

Nabil A. Siddiqui, Hailey A. Houson, Nitin S. Kamble, Jose R. Blanco, Robert E. O’Donnell, Daniel J. Hassett, Suzanne E. Lapi, Nalinikanth Kotagiri

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Figure 2

64Cu-YbT specifically identifies FyuA-expressing bacteria in vivo.

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64Cu-YbT specifically identifies FyuA-expressing bacteria in vivo.
PET/...
PET/CT images of 64Cu-YbT 24 hours after administration in mice infected with (A) S. aureus and E. coli UTI89, (B) E. coli Nissle WT and E. coli Nissle FyuA-KO mutant (ΔfyuA), (C) S. aureus and K. pneumoniae, (D) P. aeruginosa and E. coli UTI89, and (E) live and heat-killed E. coli UTI89. PET/CT images of 18F-FDG 2 hours after administration in mice infected with (F) S. aureus and E. coli UTI89 and (G) P. aeruginosa. (H) Ex vivo biodistribution of 64Cu-YbT 24 hours and 18F-FDG 2 hours after administration in infected mice muscles. Note: arrows indicate sites of bacterial injection. Data are presented as mean ± SD (n = 3) and were analyzed by Greenhouse-Geisser’s 1-way ANOVA with Dunnett’s multiple-comparison test. **P < 0.01. NS, not significant.

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