A high-throughput screening method identifies effective antimicrobial peptides, enhancing their development for treating bacterial infections.
Antimicrobial peptides (AMPs) are key to innate immunity but face challenges in rational design due to their diversity and complex mechanisms. The lack of sensitive and full function-based high-throughput screening methods for AMP variants has further impeded systematic exploration and optimization. To address this, we developed a high-throughput screening method for AMPs integrating SpyTag/SpyCatcher click biology and fluorescence resonance energy transfer (FRET). Attributing to the ultrahigh reaction rate and specificity of the SpyTag/SpyCatcher pair, this screening method allows real-time fluorometric detection of the cell lytic activity of AMPs against their natural targets, i.e., bacterial cells. Applied to an indolicidin proline-scanning library, this approach identified variants with enhanced activity against E. coli and B. subtilis. Collectively, this work establishes a function-based, high-throughput screening platform for AMPs that can fully reflect their functional complexity, thereby providing an efficient and scalable tool for screening AMP libraries and facilitating data-driven optimization and functional analysis.
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Li et al. (2026) studied this question.
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