We are interested in the virulence mechanisms used by pathogenic bacteria to infect hosts. Comparative studies based on genome sequencing of multiple pathogenic strains have suggested that bacterial species possess a pan-genome that is much larger than the genome of any single bacterium. We focus on the interaction between Pseudomonas syringae and plants. P. syringae delivers type III effector proteins into host plant cells using an evolutionarily conserved type III secretion system. This genus of pathogenic bacteria provides an excellent set of genomic and genetic tools to analyze co-evolution of host and pathogen, from the level of genome organization and horizontal gene flow down to the level of the interaction between pathogen virulence proteins and their host targets. Animal pathogens that utilize the type III secretion system include Salmonella spp., Yersinia spp., Shigella spp. and enteropathogenic E. coli. Thus, our results will inform both evolutionary and mechanistic studies of these bacteria and their animal hosts, including humans.
We optimized methods to rapidly identify P. syringae type III effector genes and their products. We continue to use functional genomics and high throughput “next generation” genome sequencing to dissect both the mechanisms and evolution of virulence in P. syringae. We will add, in this competitive renewal, a significant component dedicated to the application of comparative genomics and molecular evolutionary methods to identify novel candidate virulence genes. Our ultimate goal is to identify the pan genome of P. syringae and characterize both type III effectors and novel virulence factors across this pan-genome.
We initially chose a set of 14 phylogenetically diverse pathovars (strains) of P. syringae, including the three sequenced strains, that infect a phylogenetically broad set of host plant genera for our first sets of analysis. We expanded that target set to 19 to include newly defined outlier sub-clades of the genus. Based on MLST data, the time of divergence of the core genomes of these 14 isolates appears to be less than that between E. coli and Salmonella.
There is evidence that host targets of type III effectors are components of host disease resistance signaling networks. This concept has already informed studies on the animal innate immune system. Hence, our work has, and will continue to broaden the understanding of pathogen resistance signaling networks in various hosts. Because P. syringae is pathogenic on a variety of distantly related plant hosts, our system has advantages over models of type III pathogenesis of animals, which generally focus on strains pathogenic on related (mammalian) hosts.
This project is part of the NIH Program ‘Evolution of Infectious Diseases’