A Novel In Silico Method for Molecular Mimicry Detection Finds a Formin with the Potential to Manipulate the Maize Cell Cytoskeleton

Abstract

Molecular mimicry is one of the evolutionary strategies that parasites use to manipulate the host metabolism and perform an effective infection. This phenomenon has been observed in several animal and plant pathosystems. Despite the relevance of this mechanism in pathogenesis, little is known about it in fungus-plant interactions. For that reason, we performed an in silico method to select plausible mimicry candidates for the Ustilago maydis-maize interaction. Our methodology uses a tripartite sequence comparison between the parasite, the host and non-parasitic organisms’ genomes. Furthermore, we use RNA-seq information to identify gene co-expression, and we determine subcellular localization to detect potential cases of co-localization in the imitator-imitated pairs. With these approximations, we found a putative extracellular formin in U. maydis with the potential to rearrange the host cell cytoskeleton. In parallel, we detect at least two maize genes involved in the cytoskeleton rearrangement differentially expressed under U. maydis infection; thus, this find increases the expectation for the potential mimicry role of the fungal protein. The use of several sources of data led us to develop a strict and replicable in silico methodology to detect molecular mimicry in pathosystems with enough information available. Furthermore, this is the first time that a genome-wide search has been performed to detect molecular mimicry in a U. maydis-maize system. Additionally, to allow the reproducibility of this experiment and the use of this pipeline, we create a Web server called Molecular mimicry finder, available in https://bioquimio.udla.edu.ec/molecular-mimicry/

The search for molecular mimicry in proteins carried by extracellular vesicles secreted by cells infected with Plasmodium falciparum

“…The structural similarities can be observed in Figure 2 and for all the candidates, the superimpositions are remarkable. Said similarities alone do not imply functional molecular mimicry; other factors like subcellular space co-localization with the imitated molecule or the correct expression timing should be considered [ 30 ]. For the candidates, the opportunity to be carried by EVs makes them able to locate in several subcellular compartments at different times, allowing them to imitate several molecules.…”

EMoMiS: A Pipeline for Epitope-based Molecular Mimicry Search in Protein Structures with Applications to SARS-CoV-2

“…Many examples of the sequence similarity approach adapted for molecular mimicry searches can be found in the literature. Examples include the study of virulence mechanisms of pathogenic bacteria (Doxey and McConkey, 2013), fungus-plant interactions induced by cross-reactivity (Armijos-Jaramillo et al ., 2021), and pathogenicity of Clostridium botulinum ATCC 3502 to the human host (Bhardwaj et al ., 2018). Another approach for molecular mimicry search is to look for similar structural motifs (Kristensen et al ., 2006).…”

Epitopedia: identifying molecular mimicry between pathogens and known immune epitopes

“…To the best of our knowledge there are currently no computational programs or pipelines readily available for the prediction of molecular mimicry of known epitopes, although programs exist to map peptides (mimotopes) onto the antigenic protein structure to identify a native epitope (Chen et al, 2012; Huang et al, 2008; Mayrose et al, 2007; Negi & Braun, 2009), to identify molecular mimicry in remote homologs (Armijos-Jaramillo et al, 2021), and to identify molecular mimicry in antibody-binding interfaces (Stebliankin et al, 2022).…”