Pathogen clearance by engineering novel host innate immunity (P1251)

Abstract

Abstract A few years ago, we introduced a concept that a protein chimera of pathogen recognition and lysis domains would be able to rapidly clear a broad-spectrum of pathogens [Crit Rev Immunol 2007;27(3):233-245]. For a wide variety of viral, bacterial, and fungal pathogens, appropriate recognition and lysis domains can be chosen from the host innate immune repertoire. A chimera of the recognition and lysis domains would be designed with the aid of a flexible linker to ensure synergy of the two functions and therefore, the rapid clearance of the targeted pathogen. In this work, we demonstrate the design of such a chimera and the efficacy of this chimera in clearing a plant pathogen Xylella fastidiosa (Xf) that causes diseases in multiple plants of economic importance. The most notable ones are Pierce’s disease (PD) in grape and variegated chlorosis (CVC) in citrus. Specifically, we show the construction of the transgenic grapevines expressing a protein chimera of recognition and lysis domains specific for Xf. This chimera clears Xf from the xylem (the site of colonization) and blocks the development of PD [Proc Natl Acad Sci U S A. 2012;109(10):3721-3725]. The same chimera can be applied to block CVC. Finally, we indicate how such chimeras of recognition and lysis domains can be developed to target multiple human pathogens.