Bettina C. Fries, M.D.
Antibodies to staphylococcal enterotoxin
The primary focus of my laboratory is the pathogenesis of chronic cryptococcosis. We demonstrated that C. neoformans manifests multiple phenotypes, which allows the yeast to evade the immune response. One research project focuses on the host response as well as the molecular mechanisms that allow the fungus to change. Using mouse models we established that phenotypic switching occurs in vivo and changes the outcome in chronic Cryptococcus infection. Microarray analysis of switch variants have determined that phenotypic switching to a hypervirulent switch variant involves epigenetic down regulation of several genes. We have generated knockout variants and this work confirms that a Knockout leads to hypervirulence. Now we will study the contribution of these genes to virulence and investigate molecular mechanisms that regulate this epigenetic silencing. Our work is of general importance because it studies genes that down regulate virulence rather than up-regulate virulence. We also study the inflammatory immune response to switch variants. Cytokine analysis has demonstrated that the Mucoid switch variant elicits a damage driven non-protective immune response, which manifests signs of an over-stimulated Th-2 response whereas the Smooth switch variant elicits a protective T-cell response. In addition, this laboratory has begun a bioterrorism related project. Thus, another focus of my laboratory is to study the relevance of staphylococcal toxins during natural S. aureus infection. We have generated monoclonal antibodies to staphylococcal enterotoxin B (SEB). These mAb can completely protect SEB injected mice from SEB induced shock and death. In addition we have developed a capture ELISA that allows us to measure SEB toxin in body fluids. Future studies will concentrate on making high affinity antibodies and optimize toxin neutralization of SEB in vivo.
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