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DNA probes are fragments of DNA labeled with a reporter tag to enable their detection or purification. The resulting labeled DNA probes can then hybridize to target nucleic acid sequences through complementary base-pairing, and may be used to recover or identify these regions.
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Visualizing Borrelia burgdorferi Infection Using a Small-Molecule Imaging Probe.

Madeline G Sell1, David A Alcorta2, Andrew E Padilla2

  • 1Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.

Journal of Clinical Microbiology
|April 29, 2021
PubMed
Summary

A new fluorescent probe, HS-198, targets the conserved bacterial protein HtpG to image Borrelia burgdorferi, the cause of Lyme disease. This method works even on dormant bacteria and in animal models.

Keywords:
Borrelia burgdorferiLyme diseaseheat shock proteinimaging infectionsmall moleculesmall-molecule probe

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Area of Science:

  • Microbiology
  • Medical Imaging
  • Drug Discovery

Background:

  • Current bacterial infection imaging relies on metabolic pathways, which is ineffective for dormant or low-metabolic-activity microbes.
  • Borrelia burgdorferi, the agent of Lyme disease, presents diagnostic challenges due to its variable metabolic states.

Purpose of the Study:

  • To develop a novel imaging agent for detecting Borrelia burgdorferi in all its life stages.
  • To establish a small-molecule fluorescent conjugate targeting a conserved bacterial protein for diagnostic imaging.

Main Methods:

  • Development of HS-198, a small-molecule fluorescent conjugate targeting the highly conserved bacterial protein HtpG.
  • Testing HS-198's ability to target morphologic forms of B. burgdorferi in logarithmic and stationary phases, and inactivated spirochetes.
  • In vivo imaging of B. burgdorferi in a murine infection model using systemically injected HS-198.

Main Results:

  • HS-198 selectively targets HtpG in Borrelia burgdorferi.
  • The probe successfully imaged B. burgdorferi in logarithmic, stationary, and inactivated states.
  • HS-198 enabled imaging of B. burgdorferi in postnecropsy tissue sections from infected mice.

Conclusions:

  • Small-molecule probes targeting conserved bacterial proteins offer a new strategy for noninvasive microbial identification.
  • HS-198 demonstrates potential for diagnosing bacterial infections, including Lyme disease, regardless of bacterial metabolic activity.
  • The developed probe may serve as a scaffold for targeted antimicrobial delivery to pathogens.