O-014 Bioengineering Bacterially Derived Immunomodulants A Novel Therapeutic Approach to Inflammatory Disease

• Published in: Inflammatory bowel diseases Vol. 19; pp. S8 - S9
• Main Authors: Champion, Julie, Wu, Huixia, Estrada, Lina, Ling, Kevin, Sumagin, Ronen, Parkos, Charkes, Neish, Andrew
• Format: Journal Article
• Language: English
• Published: 01.12.2013
• Subjects: Bacteria; Salmonella
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/01.MIB.0000438565.33259.df

The purpose of this study was to exploit the evolutionary relationship of gut and pathogenic bacteria to develop novel mucosal therapeutics. Certain bacterial pathogens use needle-like structures, known as the type III secretion system (T3SS) to inject preformed effector proteins directly into the cytoplasm of host cells. We have identified one of these effectors, AvrA from Salmonella, as a potential therapeutic agent for acute and chronic inflammation such as that observed in inflammatory bowel disease (IBD). In prior work, we have established that AvrA, an acetyltransferase with specificity toward MAPKK family members, decreases inflammatory signals in vitro and in fly and murine models, while remarkably is simultaneously a potent suppressor of apoptosis. We observe that AvrA nanoparticles are internalized in vitro in a variety of cell types and in vivo at significantly higher rates than soluble protein and that AvrA in the nanoparticles retains its bioactivity when delivered. Furthermore, we demonstrate antiinflammatory activity in 2 different in vivo models.