Cracking the codon code for pathogen effector secretion in host plant cells

About This Grant

Plant pathogens threaten global food security. During early infection, oomycetes and fungi, including the fungal rice destroyer Magnaporthe oryzae, often grow in intimate contact with living host plant cells. During this growth stage the pathogen deploys secreted proteins (effectors) to suppress host defenses. In turn, the plant can recognize these effectors via intracellular resistance (R) proteins to trigger immunity. However, pathogens can lose or rapidly alter effectors to enable host jumps and cause new epidemics. Identifying pathogen cytoplasmic effectors and host targets can safeguard agriculture by informing which genomic features to deploy against which pathogen populations. Unfortunately, however, new fungal cytoplasmic effectors are difficult to predict from genomes because they are highly diverse and lack recognizable features. Furthermore, preventing disease beyond effector discovery and blockage requires mechanistic details, which are sparse. This proposal will address these knowledge gaps by leveraging recent key findings related to the role of mRNA translation in effector secretion and infection success, to clarify the rules for effector evolution, discovery and deployment that will be applicable across a broad class of pathogens. The experimental and educational objectives of this project will be integrated to inspire undergraduates to excel in research, enable graduate students to develop as mentors, and provide all students with the tools to succeed in STEM careers. Suppression of host innate immunity by secreted pathogen effector proteins is at the heart of the plant-microbe interaction, but in eukaryotes, mechanistic details regarding their secretion are sparse, thereby slowing progress towards identifying novel sources of host resistance. Effector secretion occurs via two routes: apoplastic effectors are secreted by the conventional ER-Golgi pathway, while cytoplasmic effectors destined for the host plant cell are secreted via the Golgi-bypass unconventional protein secretion (UPS) pathway. How effector proteins are sorted into the Golgi-bypass UPS pathway is not known. The principal investigators recently showed that M. oryzae cytoplasmic effector secretion (but not apoplastic effector secretion) is controlled at the level of AA-ending codon decoding, suggesting a translation-mediated mechanism discriminating apoplastic effectors from cytoplasmic effectors. Building on this finding, they hypothesize that AA-ending codons precisely control cytoplasmic effector mRNA translation speeds to ensure successful host infection. Using live-cell imaging and M. oryzae strains expressing a plethora of codon recoded cytoplasmic effector genes, the researchers seek to show precisely how effector codon usage and mRNA translation rates can i) aid in effector discovery, ii) fine tune effector secretion to maintain host-microbe interfacial integrity, and iii) be exploited as tools to identify the elusive fungal cytoplasmic effector secretion signal. By investigating this novel codon-mediated connection between mRNA translation and unconventional protein secretion, the work will generate new insights into the molecular mechanisms establishing host-microbe interactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.