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Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
3
Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA
4
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Pathogens 2013, 2(2), 383-401; https://doi.org/10.3390/pathogens2020383
Received: 2 April 2013 / Revised: 13 May 2013 / Accepted: 14 May 2013 / Published: 23 May 2013
(This article belongs to the Special Issue Pathogen Infection Models)
Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections. View Full-Text
Keywords: Burkholderia mallei; CpG; immunomodulation; in vivo imaging; infrared fluorescent imaging Burkholderia mallei; CpG; immunomodulation; in vivo imaging; infrared fluorescent imaging
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Mott, T.M.; Johnston, R.K.; Vijayakumar, S.; Estes, D.M.; Motamedi, M.; Sbrana, E.; Endsley, J.J.; Torres, A.G. Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques. Pathogens 2013, 2, 383-401.

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