Manipulation of Host Immunity by Bacterial Effectors in Arabidopsis

He, Sheng

Abstract

The long-term goal of this research is to elucidate how bacterial pathogens suppress host innate immunity to cause disease using the model Arabidopsis-Pseudomonas syringae pathosystem. Through evolution, plants and humans have developed powerful immune systems to effectively prevent colonization of most microbes; however, they can be highly susceptible to a subset of microbes that have evolved specific mechanisms to overcome host immunity. One such mechanism, used by many human and plant pathogenic bacteria, is the type III secretion system, which injects potent effector proteins into the host cell to promote infection. Recent studies have begun to show exciting results regarding how these bacterial effectors attack the host immune system. In particular, the Pseudomonas syringae effector HopM1 degrades a regulator (MIN7) of immunityassociated host vesicle traffic in a host 26S proteasome-dependent manner. Although HopM1 is the first bacterial effector reported to trick the host ubiquitination/26S proteasome system into degrading a host protein, the exact mechanism of HopM1 action remains to be elucidated. HopM1 is functionally redundant to another P. syringae effector, AvrE, which contains two WxxxE motifs found in many effectors of human pathogenic bacteria. The specific goals of this project are: (i) to characterize the mechanism by which HopM1 manipulates the host ubiquitination/proteasome system to degrade MIN7; (2) to conduct live cell imaging to determine dynamic subcellular focal accumulation of MIN7 during the immune response; (3) to identify immunityassociated GTPases regulated by MIN7; and (4) to characterize the host targets of AvrE. An integrative approach using molecular genetic, cell biological, transgenic, microscopic, and pathogenesis methods will be taken to achieve these goals. Elucidating the mechanisms by which HopM1 and AvrE modulate host vesicle traffic promises to illuminate common and novel protein biochemistry used by different pathogens to engage eukaryotic innate immunity components, and to provide fundamental knowledge for the development of novel disease intervention strategies.

Public Health Relevance

This application describes basic research to understand how bacterial pathogens suppress host innate immunity. The knowledge gained from this research should yield broad principles for the development of novel and effective methods of disease intervention in humans and plants.