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Muthye, V.

Publications and source records attributed to Muthye, V..

2 recordsLinked to original sources

Identification of potential molecular mimicry in pathogen-host interactions

Pathogens have evolved sophisticated strategies to manipulate host signaling pathways, including the phenomenon of molecular mimicry, where pathogen-derived biomolecules imitate host biomolecules. In this study, we used a sequence-based bioinformatics pipeline to identify potential molecular mimicry candidates between humans and 32 pathogenic species--bacteria, fungi, protozoa, and helminths--of global health importance. We observed considerable variation in the number of mimicry candidates across pathogenic species, with pathogenic bacteria exhibiting fewer candidates compared to fungi and protozoans. Further analysis revealed that the candidate mimicry regions were enriched in solvent-accessible regions, highlighting their potential functional relevance. We identified a total of 1878 mimicked regions in 1439 human proteins, and clustering analysis indicated diverse target proteins across pathogen species. The human proteins containing mimicked regions revealed significant associations between these proteins and various biological processes, with an emphasis on host extracellular matrix organization and cytoskeletal processes. However, immune-related proteins were underrepresented as targets of mimicry. Our findings provide insights into the broad range of host-pathogen interactions mediated by molecular mimicry and highlight potential targets for further investigation. This comprehensive analysis contributes to our understanding of the complex mechanisms employed by pathogens to subvert host defenses and promotes the development of novel therapeutic strategies.

microbiology↗

Proteome-wide comparison of tertiary protein structures reveal extensive molecular mimicry in Plasmodium-human interactions

Molecular mimicry is a strategy used by parasites to escape the host immune system and successfully transmit to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, with advances in the prediction of tertiary structural models, led by Deepminds AlphaFold, it is now possible to compare the tertiary structures of thousands of proteins from parasites and their hosts, to identify more subtle mimics. Here, we present the first proteome-level search for tertiary structure similarity between the proteins from Plasmodium falciparum and human. Of 206 P. falciparum proteins that have previously been proposed as mediators of Plasmodium-human interactions, we propose that seven evolved to molecularly mimic a human protein. By expanding the approach to all P. falciparum proteins, we identified a further 386 potential mimics, with 51 proteins corroborated by additional biological data. These findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.

bioinformatics↗