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

JCI Insight. 2021 May 24;6(10):e144880. doi: 10.1172/jci.insight.144880.

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.

Keywords: Bacterial infections; Diagnostic imaging; Infectious disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteria / chemistry
  • Bacteria / metabolism
  • Bacterial Infections* / diagnostic imaging
  • Bacterial Infections* / microbiology
  • Copper / metabolism*
  • Disease Models, Animal
  • Echocardiography
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Molecular Imaging
  • Phenols* / analysis
  • Phenols* / chemistry
  • Phenols* / metabolism
  • Positron-Emission Tomography / methods*
  • Siderophores* / analysis
  • Siderophores* / chemistry
  • Siderophores* / metabolism
  • Thiazoles* / analysis
  • Thiazoles* / chemistry
  • Thiazoles* / metabolism

Substances

  • Phenols
  • Siderophores
  • Thiazoles
  • yersiniabactin
  • Copper