Sheng Yang He is studying bacterial pathogenesis and disease susceptibility in plants, with a focus on understanding how a bacterial pathogen, Pseudomonas syringae, manipulates host cellular functions to induce disease susceptibility in plants.
Plant diseases are one of the most important causes of crop loss globally, presenting a major obstacle in sustainable production of food and energy crops that are essential for basic human nutrition and health. Understanding how pathogens cause diseases has broad implications in agriculture and human health. Historically, most studies have been focused on investigating the mechanisms by which plants resist pathogen infections, and less is known about how successful pathogens overcome plant immunity and other processes to cause diseases. Because of conceptual and mechanistic parallels in bacterial diseases in plants and humans, elucidating the molecular bases of plant disease development has the potential to enrich the fundamental knowledge of infectious disease biology that is needed to develop innovative strategies to combat a variety of pathogens.
Currently, we use a model pathosystem, the Arabidopsis thaliana-Pseudomonas syringae interaction, for our studies. In this model interaction, both the host and the pathogen are genetically and genomically tractable, making it an excellent system in which to elucidate many of the basic principles that govern pathogenesis in plant hosts. To cause disease, P. syringae bacteria produce a variety of virulence factors, including numerous "effector" proteins that are secreted through the type III protein secretion system (T3SS), and the phytotoxin coronatine, which functions as a molecular mimic of the plant hormone jasmonate. We have made steady progress in the understanding of how these virulence factors manipulate host innate immunity, jasmonate signaling, vesicle trafficking, and stomatal functions.
Bacterial Effector Proteins
The bacterial T3SS delivers many effector proteins into plant and mammalian cells to promote disease. Our early work revealed the secretion function and part of the supramolecular structure of the T3SS of P. syringae. More recently, our work contributed to the discovery of two basic functions of P. syringae effector proteins: (i) suppression of plant immune responses and (ii) creation of an aqueous apoplast in which bacteria multiply in infected plant leaves (Figure 1). Over the years, we have studied a number of different P. syringae effectors (e.g., AvrPto, HopAO1, HopZ1, HopM1, AvrE, HopO1-1). Our current effort is directed at understanding how these various effectors contribute to disease development, with the hope that, one day, we could achieve the challenging ultimate goal of reconstituting disease susceptibility using Arabidopsis mutants that could recapitulate the key virulence activities of P. syringae effectors.
Because of the central role of the T3SS and effectors in causing bacterial infections in plants and humans, there have been various efforts to inactivate this system as a broadly applicable strategy for bacterial disease control. We are currently looking into natural host defenses that could be aimed at the T3SS. Overall, we hope that our basic research on the T3SS and bacterial effectors, in the long term, may lead to development of innovative strategies for bacterial disease control.
Jasmonate Signaling in Plants
For many years, we have been interested in identifying the host target of coronatine, a toxin produced by P. syringae. Coronatine shares striking structural similarities to the plant hormone jasmonate, which plays an important role in plant growth, development, and immunity. A few years ago, we used coronatine as a molecular probe to identify key regulators (e.g., JAZ repressors) of jasmonate signaling and components of the JAZ-COI1 jasmonate receptor complex (Figure 2).
Our current work is aimed at achieving a deep understanding of the jasmonate signaling pathway, with the goal of modifying this pathway for enhanced pathogen resistance. First, we are working toward determining the crystal structure of the MYC/JAZ complex to further our understanding of how JAZ repressors inhibit MYC transcription factors. Second, we are studying the molecular basis underlying the well-known “growth-defense tradeoff," in which activation of jasmonate defense signaling is accompanied by dramatic inhibition of plant growth. Our results so far suggest that a direct interaction between JAZ repressors of jasmonate signaling and DELLA repressors of gibberellic acid (a major plant growth hormone) constitutes part of a conserved mechanism to prioritize growth vs. defense in plants. Third, we are devoting efforts to engineering the jasmonate receptor to allow for sufficient endogenous jasmonate signaling but greatly reduced sensitivity to coronatine toxin to demonstrate the feasibility of host target modifications as a new way of generating disease-resistant plants.
The Immune Function of Plant Stomata
Plant stomata, formed by pairs of guard cells, are microscopic pores on the surface of all land plants. In the plant pathology discipline, it has long been assumed that stomata serve as passive portals of entry for plant pathogens, particularly bacterial pathogens. However, our work shows that plant stomata have an important immune function. Specifically, stomata close in response to plant and human pathogenic bacteria (Figure 3). Stomatal guard cells could perceive bacteria through pattern recognition receptors, such as flagellin receptor FLS2, activating a signaling cascade that requires the plant stress hormones salicylic acid.
The signal transduction pathway underlying stomatal closure to pathogens is not well characterized. We are taking several approaches to increase our understanding in this area. First, we are investigating the epistatic relationships between various signaling pathways in the stomatal guard cell. Second, we are isolating Arabidopsis mutants, based on compromised stomatal response to P. syringae bacteria, to identify new signaling components involved in the pathogen-triggered guard cell immune response. Third, we are studying in interactions between stomata and human pathogenic bacteria in the phyllosphere.
New Research Initiatives: The Next Phase of Study
Our current understanding of bacterial pathogenesis and disease susceptibility in plants remains largely one-dimensional, reflecting the heavy reliance on simplistic bilateral interactions of one pathogen and one host under static laboratory conditions. As a result, our knowledge of disease susceptibility does not accurately reflect the multi-dimensional features of plant disease development that occur in nature. To break new ground for the next phase of research on bacterial pathogenesis and disease susceptibility in plants, we have initiated two new projects:
(i) Environmental Regulation of Disease Development: We are studying the molecular bases of the effects of temperature and humidity, which are known to significantly influence disease outbreaks in crop fields.
(ii) Developing A Soil-based Gnotobiotic Plant Growth System: Our goal is to develop a gnotobiotic plant growth system (called “Flowpot”) that enables the study of plant-microbe interactions in soil substrates, in the presence or absence of the endogenous microbiome. With further optimization, we hope that the FlowPot gnotobiotic system may be broadly useful in the study of interplay between the microbiome and plant biology.
Grants from Gordon and Betty Moore Foundation, the National Institutes of Health, National Science Foundation, the National Institute of Food and Agriculture and the Department of Energy provided partial support for these projects.
As of March 11, 2016