Translational barriers to phage endolysin deployment for antimicrobial resistance control in Africa

Antimicrobial resistance (AMR) poses a rapidly escalating threat to public health, food security, and environmental sustainability across Africa, where limited diagnostic capacity, unregulated antibiotic use, and weak pharmaceutical pipelines exacerbate treatment failures. Bacteriophage-derived endolysins have emerged globally as promising next-generation antimicrobials due to their rapid bacteriolytic activity, low resistance potential, and modular engineering flexibility. Despite significant advances in endolysin discovery, engineering, and clinical translation worldwide, their deployment in Africa remains negligible. This disparity raises a critical question: why have phage endolysins not progressed beyond early-stage research in Africa despite their relevance to the continent's AMR burden? This review provides a critical analysis of the translational barriers hindering the development, adoption, and commercialization of phage endolysins for AMR control in Africa. Drawing on published African and global literature, we identify interconnected scientific, infrastructural, regulatory, economic, and policy-related constraints that limit progress from laboratory discovery to real-world application. Key barriers include limited genomic and protein engineering capacity, absence of regional phage and endolysin repositories, inadequate biosafety and regulatory frameworks for biologics, dependence on imported reagents and expression systems, and weak integration of lysin technologies into national AMR and One Health action plans. We further highlight a mismatch between globally prioritized lysin targets and Africa's dominant clinical, agricultural, and environmental pathogens. By reframing the African endolysin landscape through a translational failure lens, this review moves beyond descriptive summaries to propose actionable pathways for overcoming these barriers. We outline strategic priorities for capacity building, regulatory harmonization, funding mechanisms, and regional collaboration necessary to enable Africa's participation in the global endolysin pipeline. Addressing these translational bottlenecks is essential for ensuring equitable access to lysin-based antimicrobials and for positioning Africa as an active contributor to next-generation AMR solutions rather than a passive end-user.