1. Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice.
- Author
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Welling MM, de Korne CM, Spa SJ, van Willigen DM, Hensbergen AW, Bunschoten A, Duszenko N, Smits WK, Roestenberg M, and van Leeuwen FWB
- Subjects
- Animals, Humans, Mice, Molecular Imaging, Organotechnetium Compounds chemistry, Peptide Fragments chemistry, Staphylococcus aureus growth & development, Thigh diagnostic imaging, Tissue Distribution, Tomography, Emission-Computed, Single-Photon, Urine chemistry, Urine microbiology, Carbocyanines chemistry, Organotechnetium Compounds administration & dosage, Peptide Fragments administration & dosage, Staphylococcal Infections diagnostic imaging, Staphylococcus aureus pathogenicity
- 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,
99m Tc-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 with99m Tc-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 the99m Tc-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 with99m Tc-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.- Published
- 2019
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