A common mechanism for virulence protein entry

When the data sets and tools are in place scientists can push ahead to understand the biology of plant disease. One of the fundamental questions they want to address is how do oomycete pathogens break and enter plant cells? The answer lies with effector molecules, proteins that can manipulate the physiology of their hosts making them more susceptible to infection. Recently, VBI researchers have identified the region of a large family of virulence proteins in oomycete plant pathogens that enables these proteins to invade the cells of their hosts. The protein region contains “signature” sequences that, in the one-letter code used to describe the amino acids making up proteins, are referred to as RXLR and dEER motifs. The RXLR and dEER motifs are essential to carry the virulence proteins across the membrane surrounding plant cells without any additional machinery from the pathogen. Once inside the plant cell, the proteins suppress the immune system of the plant allowing the infection to progress.

VBI scientists discovered the importance of the RXLR and dEER motifs for infection using an ingenious device for introducing DNA into living tissues that was invented by a Virginia Tech undergraduate, Shiv Kale. Kale, who is now a graduate student in Dr. Tyler’s laboratory and was recently awarded a National Science Foundation Graduate Research Fellowship award, says: “The double-barreled Gene Gun enabled us to make much more accurate measurements of effector proteins than were previously possible, which made it practicable to measure the action of the RXLR and dEER motifs.”

Double Shot Gene Gun

When the researchers probed the published genome sequences of Phytophthora ramorum and Phytophthora sojae using bioinformatic tools that can look for RXLR and dEER motifs, they identified an enormous superfamily of pathogen genes involved in the infection of plants - the Avh superfamily. The results confirm that a single gene from a common ancestor of the both pathogen species has spawned hundreds of very different, fast-evolving genes that encode for these highly damaging effector proteins. Given that there are more than 90 species of Phytophthora pathogens, these findings imply that there are more than 30 000 members of this deadly superfamily within the genus Phytophthora.

The road ahead: Future interventions

The investment in building a systems-wide understanding of Phytophthora-plant interactions is starting to pay dividends not only for future disease intervention strategies in plants but also for countermeasures relevant to human disease.

VBI Professor Brett Tyler remarks: “We have recently shown that RXLR and dEER motifs are crucial for entry into both plant and animal cells. The finding that virulence proteins from oomycetes, the malaria parasite Plasmodium, and certain fungi use the same entry mechanism means that we may be able to use the same or similar drugs to block infection in all three groups of pathogens.”

The reward for finding a common mechanism for entry of pathogen proteins into the host cells of animals, humans, and plants could be considerable. Says Tyler: “We have recently discovered a small molecule that can block the entry of effector proteins into the cell. This significant observation paves the way for the identification of a new class of therapeutic agents that can protect plants, animals and humans from deadly oomycete, fungal, and parasite infections.”