Modes of action of antifungal defensins and defensin-like peptides and their use in development of disease resistant crops.

Research in the Shah Lab is directed toward obtaining a better understanding of the innate immunity mechanisms through which plants protect themselves from fungal pathogens. Critical discoveries from our group include the finding that plants produce a large number of small cysteine-rich antifungal peptides known as defensins and

defensin-like peptides. Fundamental basic science approaches using modern techniques of protein biochemistry, microbiology, cell biology and plant pathology are applied to the analysis of the antifungal properties and modes of action of these peptides against economically important fungal pathogens of plants with the goal of translating this information into improved disease control for crop species. 

Plant defensins are naturally occurring ribosomally synthesized cysteine-rich antifungal peptides with a tetradisulfide array. These peptides vary greatly in sequence but share common structural similarity. We have studied the antifungal activity and mechanisms of action of a number of these peptides from a model legume Medicago truncatula. These peptides exhibit potent antifungal activity at low micromolar or submicromolar concentrations against a broad range of plant fungal pathogens, but their mechanisms of action are strikingly different. The mode-of-action studies have revealed that these peptides permeabilize the plasma membrane of fungal pathogens, induce the production of reactive oxygen species and gain entry into fungal cells. However, they bind to different phospholipids in the membranes. Surprisingly, closely related fungal pathogens also vary in their responses to a specific plant defensin. 

Leguminous plants form a symbiotic relationship with nitrogen-fixing bacteria known as Rhizobium spp. These bacteria undergo dramatic differentiation to bacteroids in the indeterminate nodules of legumes such as Medicago truncatula and Cicer arientum.  During this differentiation process, nodules of these plants express a large number of small cysteine-rich defensin-like peptides. Several of these peptides are cationic that are capable of inhibiting fungal and bacterial pathogens at low micromolar concentrations. Shah Lab is investigating antimicrobial activity, structure-activity relationships and mechanisms of action of these defensin-like peptides containing 2-or 3 disulfide bonds. The current studies in the lab are focused on characterizing molecular processes involved in facilitating fungal cell entry of these peptides and identifying their intracellular targets. Numerous questions remain in this field and are the topics of ongoing research in the lab. 

The ultimate goal in the Shah Lab is to characterize precise molecular events governing the antifungal activity of defensins and defensin-like peptides from plants and to translate this information for effective and sustainable control of fungal diseases in the field. The Shah Lab is also exploring the potential of these peptides for commercial development as peptide-based spray-on antifungal agents in crops.