Pathogen clearance by engineering of novel innate immune defense (INM3P.414)

Abstract

Abstract Pathogens circumvent host immune defense to propagate their lifecycle. We have been studying the mechanisms of pathogen-induced host cell death to develop a robust strategy for pathogen clearance. The strategy involves designing and developing a protein chimera with one domain for recognizing conserved pathogen membrane elements and another for lysing the pathogen membrane. This dualistic synergy of recognition and lysis permits rapid pathogen clearance thereby preventing host cell death and disease development. This strategy has been successfully applied to counteract bacterial infections and diseases in grape, citrus, and tobacco. We have engineered a chimera consisting of protease (recognition domain) and cecropin (lysis domain) to prevent Pierce’s disease, a deadly disease in grape caused by Xylella fastidiosa. We have shown that transgenic plants expressing the chimera of protease and cecropin effectively clear Xylella fastidiosa from sites of colonization. We have also designed a protein chimera of thionin (with both recognition and lysis domains) and a synthetic lytic peptide. We have shown that this same chimera prevents citrus canker which is caused by Xanthamonas axonopodis citri and wildfire disease in tobacco which is caused by Pseudomonas syringe pv. tobaci. This protein engineering strategy appears to be an effective therapy against a broad spectrum of plant pathogens. A similar approach is now being evaluated against multiple human pathogens.