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

Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice.

Author information

1
Interventional Molecular Imaging Laboratory, Department of Radiology , Leiden University Medical Center , 2333ZA Leiden , The Netherlands.
2
Department of Parasitology and Department of Infectious Diseases , Leiden University Medical Center , 2333ZA Leiden , The Netherlands.
3
Laboratory of BioNanoTechnology, Department of Agrotechnology and Food Sciences , Wageningen University & Research , 6708PB Wageningen , The Netherlands.
4
Department of Medical Microbiology, Section Experimental Bacteriology , Leiden University Medical Center , 2333ZA Leiden , The Netherlands.

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

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