Richard W Davis1, Heather Eggleston1, Frances Johnson1, Matthias Nahrendorf2, Paul E Bock3, Tiffany Peterson1, Peter Panizzi4. 1. Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, 4306 Walker Building, Auburn, AL, 36849, USA. 2. Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge St., Boston, MA, 02114, USA. 3. Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 4. Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, 4306 Walker Building, Auburn, AL, 36849, USA. panizzi@auburn.edu.
Abstract
PURPOSE: Generation of plasmin in vivo by Streptococcus pyogenes is thought to localize the active protease complexes to the pathogen surface to aid in tissue dissemination. Here, we chose to follow cutaneous streptococcal infections by the use of non-invasive bioluminescence imaging to determine if this pathogen can be followed by this approach and the extent of bacterial spread in the absence of canonical plasminogen activation by streptokinase. PROCEDURES: Mice were injected subcutaneously with either bioluminescent strains of streptococci, namely Xen20 and Xen10 or S. pyogenes ALAB49. Bioluminescence imaging was performed daily and results were correlated with microbiological and histological analyses. RESULTS: Comparative analysis of chronologic non-invasive datasets indicated that Xen20 did not disseminate from the initial infection site. Contrary to this, microbiological and histological analyses of Xen20 mice for total bacterial burden indicated sepsis and widespread pathogen involvement. CONCLUSIONS: The use of bioluminescence in microbe-based studies requires genomic and pathologic characterization to correlate imaging results with underlying pathology.
PURPOSE: Generation of plasmin in vivo by Streptococcus pyogenes is thought to localize the active protease complexes to the pathogen surface to aid in tissue dissemination. Here, we chose to follow cutaneous streptococcal infections by the use of non-invasive bioluminescence imaging to determine if this pathogen can be followed by this approach and the extent of bacterial spread in the absence of canonical plasminogen activation by streptokinase. PROCEDURES: Mice were injected subcutaneously with either bioluminescent strains of streptococci, namely Xen20 and Xen10 or S. pyogenes ALAB49. Bioluminescence imaging was performed daily and results were correlated with microbiological and histological analyses. RESULTS: Comparative analysis of chronologic non-invasive datasets indicated that Xen20 did not disseminate from the initial infection site. Contrary to this, microbiological and histological analyses of Xen20 mice for total bacterial burden indicated sepsis and widespread pathogen involvement. CONCLUSIONS: The use of bioluminescence in microbe-based studies requires genomic and pathologic characterization to correlate imaging results with underlying pathology.
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