Fang Lab publication

Biomimetic virulomics for capture and identification of cell-type specific effector proteins

Lapek, J.; Fang, R.H.; Wei, X.; Li, P.; Wang, B.; Zhang, L.; Gonzalez, D.

ACS Nano2017Vol. 1111831-11838

Summary

This study develops a proteomics workflow for finding pathogen effector proteins that act on particular host-cell types. The motivating problem is that genome-centered screens can miss important virulence factors when gene presence or expression does not correspond closely to the functional proteome. The authors created “Biomimetic Virulomics,” combining cell-derived biomimetic affinity materials with multiplexed quantitative proteomics. These materials provide host-cell-like binding surfaces that enrich proteins according to relevant biological interactions, after which proteomic analysis identifies captured candidates at scale. The approach was applied to both prokaryotic and eukaryotic pathogens and recovered known virulence factors in a cell-type-guided, high-throughput manner. The researchers also characterized the membrane-protein composition of the biomimetic materials used for capture. The principal contribution is a functional enrichment strategy that narrows virulence-factor discovery toward proteins capable of engaging a selected cellular interface, potentially generating more relevant drug targets than sequence analysis alone. Limitations are substantial: the abstract does not specify pathogen panels, numbers of candidates, enrichment accuracy, false-positive rates, independent functional validation, or comparison with existing screens. Capture indicates affinity, not necessarily causal pathogenic activity, and translational drug-discovery value remains prospective.