Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice

ACS Infect Dis. 2019 Jul 12;5(7):1160-1168. doi: 10.1021/acsinfecdis.9b00015. Epub 2019 May 2.

Abstract

There is a need to develop diagnostic and analytical tools that allow noninvasive monitoring of bacterial growth and dissemination in vivo. For such cell-tracking studies to hold translational value to controlled human infections, in which volunteers are experimentally colonized, they should not require genetic modification, and they should allow tracking over a number of replication cycles. To gauge if an antimicrobial peptide tracer, 99mTc-UBI29-41-Cy5, which contains both a fluorescent and a radioactive moiety, could be used for such in vivo bacterial tracking, we performed longitudinal imaging of a thigh-muscle infection with 99mTc-UBI29-41-Cy5-labeled Staphylococcus aureus. Mice were imaged using SPECT and fluorescence-imaging modalities at various intervals during a 28 h period. Biodistribution analyses were performed to quantitate radioactivity in the abscess and other tissues. SPECT and fluorescence imaging in mice showed clear retention of the 99mTc-UBI29-41-Cy5-labeled bacteria following inoculation in the thigh muscle. Despite bacterial replication, the signal intensity in the abscess only modestly decreased within a 28 h period: 52% of the total injected radioactivity per gram of tissue (%ID/g) at 4 h postinfection (pi) versus 44%ID/g at 28 h pi (15% decrease). After inoculation, a portion of the bacteria disseminated from the abscess, and S. aureus cultures were obtained from radioactive urine samples. Bacterial staining with 99mTc-UBI29-41-Cy5 allowed noninvasive bacterial-cell tracking during a 28 h period. Given the versatility of the presented bacterial-tracking method, we believe that this concept could pave the way for precise imaging capabilities during controlled-human-infection studies.

Keywords: SPECT; bacterial infection; cell-tracking; fluorescence; multimodal; ubiquicidin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbocyanines / chemistry*
  • Humans
  • Mice
  • Molecular Imaging
  • Organotechnetium Compounds / administration & dosage*
  • Organotechnetium Compounds / chemistry
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / chemistry
  • Staphylococcal Infections / diagnostic imaging*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / pathogenicity*
  • Thigh / diagnostic imaging
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Urine / chemistry
  • Urine / microbiology

Substances

  • Carbocyanines
  • Organotechnetium Compounds
  • Peptide Fragments
  • cyanine dye 5
  • technetium 99m ubiquicidin(29-41)