Molecular Shape-Shifting Qualities Of Plants And Pathogens Determine Survival

What makes a pathogen successful? What determines a plant’s ability to defend itself against an invader? The outcome of a myriad of encounters between plants and their pathogens have preoccupied humans since the dawn of agriculture. Crop diseases have a devastating economic impact that reaches billions of dollars annually and are a recurring global threat to food production (Horvath 2018). Discovering the key that unlocks the code of plant-pathogen interactions has motivated extensive research on the molecular determinants of pathogen virulence and plant resistance, and on devising strategies to apply this knowledge in modern agricultural practices.

A healthy plant can defend itself against most pathogens by quickly detecting and eliminating an invader. At the basis of this remarkable function is the plant immune system. Receptor proteins located in the cellular plasma membrane continuously survey the extracellular space for pathogen-associated molecules, which they recognize and bind with high affinity(Dangl and Jones 2001). Upon pathogen detection, plant receptors activate a suite of cytosolic protein kinases which self-assemble and activate each other sequentially in intracellular signal transduction pathways (Popescu et al. 2009, Popescu 2016). Immediately, the signal reaches the nucleus where special transcription factors alter the expression levels of hundreds of genes and consequently, modify cellular structure and milieu to damage and eliminate the pathogen.

Some bacterial pathogens produce large numbers of extracellular virulence factors in the course of infection and associate their production with specific time points in the progression of the plant immune response (Asai and Shirasu 2015, Toruño et al. 2016). Virulence factors help pathogens evade the immune response and proliferate in plant tissues. We have only a limited understanding of how virulence factors operate once secreted into the plant cell, the identity of the immune components they interact with, and their overall impact on the immune system.

In a recent study, we applied a systems biology approach to understanding how virulence factors produced by the bacterial pathogen Pseudomonas syringae interact with plant kinases and modify the structure of signal transduction networks (Brauer et al. 2018).

Out of the approximately one thousand protein kinases encoded by a plant genome, how many are attacked and inactivated by virulence factors is an open question.  In the first set of experiments, we identified tomato protein kinases that interacted with P. syringae virulence factors. A large number of kinase targeted by the virulence factors tested and a high degree of similarity in target preference among these factors– were some of our findings with far-reaching implications. As such, it is highly probable that when attempting to subvert the plant immune system, pathogens utilize redundant means to attack plant molecules. From an evolutionary perspective, virulence factors having a broad range of host targets are likely to confer an extraordinary advantage to a pathogen, which could quickly adjust to a new host and expand its host range. If indeed pathogens are subverting the immune system using redundancy in target selection as a key strategy, what are the counter-mechanisms utilized by plants to fight off pathogen infection?

While more research is needed for a complete answer to this question, insights on the probable coping strategies of plants were gained from experiments where plants were infected with P. syringae strains having absent or limited ability to produce virulence factors. We observed that plants activated larger networks of protein kinases when infected with P. syringae strains producing one single virulence factor, compared to plants infected with a non-producing strain. From a systems biology perspective, a complex signaling network composed of multiple parallel pathways converging into a common set of defense genes would be more efficient in fighting off a highly virulent pathogen. Plants may be able to accurately assess the type of pathogen invader and adjust the strength of their immune response by activating compensatory pathways when necessary. Thus, the capacity to rapidly adjust the topology of signaling networks emerges as one of the key plant strategies to undermine virulence factors.

Interestingly, a closer look at kinases in the signaling networks triggered by virulence-producing P. syringae strains uncovered a surprising fact. Alongside the immunity-promoting kinases were a few others which were, instead, increasing plant susceptibility. It’s as though infected plant cells react to virulence factors asexpected– by increasing their immune capacity – but, at the same time, they also become a favorable host for the pathogen. Decades ago, scientists exploring the mechanisms of pathogenicity in bacteria advanced the phenomenon of the ‘host as a growth medium’ whereby pathogens undermine the infected host defenses to extract nutrients (Garber 1960).  In modern times, relatively few studies have focused on the ability of pathogens to manipulate plant cells for nutrient gain (van Schie and Takken 2014). Information on the identity of the molecules and signaling pathways that are likely to act as susceptibility factors in a plant under infection can help us devise approaches to deter pathogens’ actions and tip the balance in favor of the plant.

The molecular dialogue between a plant and a pathogen is intricate. Our work underscores the remarkable plasticity of the cellular networks that operate at the interface between plants and their pathogens. The shape-shifting signaling networks activated by plants appear to be the consequential reaction to the pathogen’s equally malleable virulence factors. The ultimate goal remains to figure out the general rules of this plant-pathogen communication code, as they will inform our future strategies for crop disease-control.

References:

1. Asai, S. and K. Shirasu (2015). “Plant cells under siege: plant immune system versus pathogen effectors.” Current opinion in plant biology 28: 1-8.
2. Brauer, E. K., G. V. Popescu, D. K. Singh, M. Calviño, K. Gupta, B. Gupta, S. Chakravarthy and S. C. Popescu (2018). “Integrative network-centric approach reveals signaling pathways associated with plant resistance and susceptibility to Pseudomonas syringae.” PLOS Biology 16(12): e2005956.
3. Dangl, J. L. and J. D. Jones (2001). “Plant pathogens and integrated defence responses to infection.” nature 411(6839): 826.
4. Garber, E. (1960). “The host as a growth medium.” Annals of the New York Academy of Sciences 88(1): 1187-1194.
5. Horvath, D. M. (2018). “Putting Science into Action to Address Threats to Food Security Caused by Crop Diseases.” Outlooks on Pest Management 29(3): 130-133.
6. Popescu, S. C. (2016). “Protein networks–A driving force for discovery in plant science.” Current Plant Biology 5(1): 1.
7. Popescu, S. C., G. V. Popescu, S. Bachan, Z. Zhang, M. Gerstein, M. Snyder and S. P. Dinesh-Kumar (2009). “MAPK target networks in Arabidopsis thaliana revealed using functional protein microarrays.” Genes & development 23(1): 80-92.
8. Toruño, T. Y., I. Stergiopoulos and G. Coaker (2016). “Plant-pathogen effectors: cellular probes interfering with plant defenses in spatial and temporal manners.” Annual review of phytopathology 54: 419-441.
9. van Schie, C. C. and F. L. Takken (2014). “Susceptibility genes 101: how to be a good host.” Annual review of phytopathology 52: 551-581.