|Title||Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice|
|Author(s)||Welling, Mick M.; Korne, Clarize M. De; Spa, Silvia J.; Willigen, Danny M. Van; Hensbergen, Albertus W.; Bunschoten, Anton; Duszenko, Nikolas; Smits, Wiep Klaas; Roestenberg, Meta; Leeuwen, Fijs W.B. Van|
|Source||Bmc Infectious Diseases 5 (2019)7. - ISSN 1471-2334 - p. 1160 - 1168.|
|Publication type||Refereed Article in a scientific journal|
|Keyword(s)||bacterial infection - cell-tracking - fluorescence - multimodal - SPECT - ubiquicidin|
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-UBI 29-41 -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 99m Tc-UBI 29-41 -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 99m Tc-UBI 29-41 -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 99m Tc-UBI 29-41 -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.