title: Monitoring Therapeutic Treatments againstBurkholderiaInfections Using Imaging Techniques.
abstract: 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 theB. malleibioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodalin vivowhole 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 timein vivoimaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimizedin vivoimaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.).
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Mott
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.).
authors.forename: R Katie
authors.initials: RK
authors.lastname: Johnston
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.).
authors.forename: Sudhamathi
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; dmestes@uga.edu.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA; mmotamed@utmb.edu.
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.) ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Sbrana
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.).
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Endsley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; tmmott@utmb.edu (T.M.M.); rkjohnst@utmb.edu (R.K.J.); suvijaya@utmb.edu (S.V.); elsbrana@utmb.edu (E.S.); jjendsle@utmb.edu (J.J.E.) ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Torres
keywords: Burkholderia mallei; CpG; immunomodulation; in vivo imaging; infrared fluorescent imaging