Rich, K. D. | bioRxiv Science

bioRxiv2025

mimicDetector: a pipeline for protein motif mimicry detection in host-pathogen systems

MotivationMolecular mimicry is a widespread strategy used by pathogens to evade the host immune system and manipulate other host cellular processes. Detecting these events--where pathogen proteins resemble host molecules--is challenging due to limitations in the sensitivity, specificity, and scalability of current bioinformatics tools. The challenges are pronounced when identifying subtle similarities in short protein fragments. ResultsWe present mimicDetector, an optimized bioinformatic pipeline for systematically identifying protein-level molecular mimicry between pathogens and their hosts. mimicDetector builds on existing k-mer-based approaches with three key improvements: (i) improved sensitivity for short-sequence alignments using the PAM30 substitution matrix and tuned BLASTP parameters; (ii) a revised k-mer filtering strategy based on bitscore differences rather than percent identity; (iii) the removal of overly conservative homologue exclusion steps. Applied to 17 globally important pathogens, mimicDetector identified a broad and biologically plausible set of mimicry candidates, including helminth proteins mimicking components of the human complement system and a Leishmania infantum mimic of Reticulon-4, a regulator of immune cell recruitment. Availability and implementationmimicDetector is freely available at https://github.com/Kayleerich/mimicDetector/, implemented in Python, and compatible with Unix-based systems.

bioinformatics↗

bioRxiv2023

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↗