Biology subjects

Wilson, R. A.

Publications and source records attributed to Wilson, R. A..

3 recordsLinked to original sources

bioRxiv2025

AA-ending codon-based computational analyses uncover novel cytoplasmic effectors in the Magnaporthe oryzae secretome

Phytopathogens secrete diverse, sequence-unrelated effector proteins outside (apoplastic) or into (cytoplasmic) plant cells to suppress host defenses and cause devastating diseases. Effectors rapidly evolve to avoid counter-detection by the host, and fungal cytoplasmic effectors lack recognizable host cell-targeting motifs, impeding cataloguing of the full suite of host-deployed effectors encoded in pathogen genomes. In the devastating rice blast fungus Magnaporthe oryzae, cytoplasmic and apoplastic effectors are secreted by different routes, but candidates must be confirmed by fluorescent labelling, consequently few are known. AA-ending codon usage rates are the fraction of AA-ending codons as a percentage of the total number of AA- and synonymous AG-ending codons in an mRNA. In M. oryzae, high AA % rates of the corresponding mRNAs distinguished seven experimentally confirmed cytoplasmic effectors from four experimentally confirmed apoplastic effectors, but whether AA % rates can identify new effectors is unknown. Here, using computational analyses and live-cell imaging confirmation, we successfully predicted, based on AA % rates, two new cytoplasmic effectors and two apoplastic effectors in the M. oryzae secretome. Our findings support the notion that cytoplasmic effector mRNAs are globally enriched for AA-ending codons, aiding effector discovery and the search for novel sources of durable crop resistance.

plant biology↗

bioRxiv2025

Pre-clinical studies of Schistosoma mansoni vaccines: a scoping review

BackgroundSchistosomiasis is caused by infection with worms of the genus Schistosoma including S. mansoni. Over 200 million people are infected, sterile immunity does not naturally develop, and no vaccine is available. A vaccine could be a critical tool to achieve control and elimination. Numerous candidates have been tested in pre-clinical models, but there is not yet an approved vaccine. Methodology/Principal FindingsWe conducted a scoping review using a keyword search on Web of Science and a MeSH term search on PubMed. Articles were screened and included if they tested a defined vaccine candidate in a pre-clinical protection assay against S. mansoni between 1994-2024. Vaccine formulation, study design, and efficacy parameters from all articles were extracted. This data was summarised graphically, with the influence of different parameters appraised. A total of 141 candidate antigens were tested in 108 articles over the last 30 years, with most antigens tested only once and three (Sm-CatB, Sm-p80, and Sm-14) tested over 20 times. The median protective efficacy against worms was 35%. 10 antigens achieved over 60% efficacy, and only two (Sm-p80 and Sm-CatB) over 90%. Large variations in efficacy were observed with all repeatedly tested antigens, likely attributable to differing formulations and study designs. The effect of these varying parameters on the resultant efficacy was evaluated. ConclusionsA few vaccine candidates have achieved promising efficacy in pre-clinical studies. Most vaccines tested however have efficacy that falls short of that required for an impactful schistosomiasis vaccine. The diversity in study designs makes comparing vaccine targets a challenge. Use of consistent and optimized vaccine formulation (including adjuvant and platform) and study design parameters is critical to expedite the development of a schistosome vaccine. Author SummarySchistosomiasis, a major neglected tropical disease, is caused by infection with parasitic worms of the Schistosoma species, including Schistosoma mansoni. Individuals can be repeatedly re-infected, and there is no available vaccine. An initial stage of vaccine development is testing in a pre-clinical animal model. Here we have summarised tests of Schistosoma mansoni vaccines in the last three decades. 100+ vaccine candidates have been tested, with only 10 of these achieving efficacy of over 60%, and only 2 at over 90%. When the same vaccine candidate (antigen) is tested in a different formulation, or using different study design the efficacy varies greatly. We have summarised the formulations and study designs used, and highlighted how certain parameters affect efficacy. Finally, we have assembled a series of recommendations to researchers on how to perform vaccine tests in the future.

immunology↗

bioRxiv2021

Autophagy-dependent TOR reactivation drives fungal growth in living host rice cells

Eukaryotic filamentous plant pathogens with biotrophic growth stages like the devastating hemibiotrophic rice blast fungus Magnaporthe oryzae grow for extended periods in living host plant cells without eliciting defense responses. M. oryzae elaborates invasive hyphae (IH) that grow in and between living rice cells while separated from host cytoplasm by plant-derived membrane interfaces. However, although critical to the plant infection process, the molecular mechanisms and metabolic strategies underpinning this intracellular growth phase are poorly understood. Eukaryotic cell growth depends on activated target-of-rapamycin (TOR) kinase signaling, which inhibits autophagy. Here, using live-cell imaging coupled with plate growth tests and RNAseq, proteomic, quantitative phosphoproteomics and metabolic approaches, we show how cycles of autophagy in IH modulate TOR reactivation via -ketoglutarate to sustain biotrophic growth and maintain biotrophic interfacial membrane integrity in host rice cells. Deleting the M. oryzae serine-threonine protein kinase Rim15-encoding gene attenuated biotrophic growth, disrupted interfacial membrane integrity and abolished the in planta autophagic cycling we observe here for the first time in wild type.{Delta} rim15 was also impaired for glutaminolysis and depleted for -ketoglutarate. -ketoglutarate treatment of{Delta} rim15-infected leaf sheaths remediated{Delta} rim15 biotrophic growth. In WT, -ketoglutarate treatment suppressed autophagy. -ketoglutarate signaling is amino acid prototrophy- and GS-GOGAT cycle-dependent. We conclude that, following initial IH elaboration, cycles of Rim15- dependent autophagic flux liberate -ketoglutarate - via the GS-GOGAT cycle - as an amino acid-sufficiency signal to trigger TOR reactivation and promote fungal biotrophic growth in nutrient-restricted host rice cells.

plant biology↗