Identification of potential molecular mimicry in pathogen-host interactions

Author:

Rich Kaylee D.12,Srivastava Shruti12,Muthye Viraj R.12,Wasmuth James D.12ORCID

Affiliation:

1. Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada

2. Host-Parasite Interactions Research Training Network, University of Calgary, Calgary, Alberta, Canada

Abstract

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 resurrected, updated, and optimized a sequence-based bioinformatics pipeline to identify potential molecular mimicry candidates between humans and 32 pathogenic species whose proteomes’ 3D structure predictions were available at the start of this study. 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 1,878 mimicked regions in 1,439 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 we provide a resource to assist researchers in the development of novel therapeutic strategies.

Funder

Natural Sciences and Engineering Research Council of Canada

University of Calgary Eyes High doctoral student recruitment scholarship

University of Calgary Eyes High postdoctoral recruitment scholarship

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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