In vivo analysis of virulence expression in model of group A streptococcal diseas

University Of Texas Sw Med Ctr/Dallas, Dallas TX

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Abstract

The group A streptococcus (Streptococcus pyogenes, GAS) is unsurpassed among bacterial pathogens in its ability to cause a variety of skin infections ranging from the self-limiting impetigo to fulminant soft tissue destruction and necrotizing fasciitis. GAS pathogenesis is a multi-factorial process, involving numerous virulence components that are involved in the specific response of the bacteria to different environments encountered within the host. However, we know very little about when these different virulence products are produced during infection. The overall aim of this pilot proposal will be to establish an in vivo reporter system based on the Green Fluorescent Protein (GFP) to assay GAS virulence gene expression during skin disease in an animal model. The specific aims of the project will be as follows: 1. To construct GAS vectors for transcriptional fusions to gfp and test their capabilities in vitro. 2. To establish in vivo conditions for assaying GFP expression in a mouse model of streptococcal invasive skin disease. 3. To assay in vivo expression of known virulence genes in a mouse model of streptococcal invasive skin disease. These studies will hopefully lead to the establishment of a useful model system for directly examining the host/pathogen interplay between GAS and the human host during invasive skin infections.