INTRODUCTION: Antimicrobial resistance is escalating globally, while the development of new antibiotic classes has stagnated. This trend is reminiscent of the late-stage dynamics of S-curve innovation, where incremental advances no longer meet clinical needs. To overcome this impasse, disruptive innovation is required. As protein-based antibacterials, lysins represent a fundamentally different modality from traditional small-molecule antibiotics and offer new opportunities for disruptive innovation in terms of resistance development and microbiome preservation. AREAS COVERED: Sourced from a vast natural reservoir, lysins exhibit rapid, targeted bactericidal activity with low resistance potential and high specificity. Their narrow-spectrum nature supports a potential for microbiome preservation and the conceptual development of theranostic platforms for precision infectious disease management, combining ultra-fast pathogen detection with targeted therapeutic activity. EXPERT OPINION: To initiate new innovation cycles, disruptive modalities such as protein-based lysins will be needed, offering a paradigm shift in antimicrobial therapy. Their modular architecture and amenability to protein engineering enable a hit-to-lead development strategy akin to small-molecule pipelines. Their synergistic interactions with standard-of-care antibiotics and booster-like activity could facilitate incremental clinical integration into existing treatment protocols. This positioning supports regulatory acceptance and paves the way for lysins to become transformational components of precision antimicrobial therapy.
Yves Briers (Tue,) studied this question.