Making waves: Wastewater sludge holds untapped antimicrobial potential.

Wastewater treatment plants are widely recognized as critical nodes in the environmental dissemination and control of antimicrobial resistance (AMR). This risk-focused view is warranted, but incomplete. Wastewater sludge is one of the largest engineered and repeatedly accessible microbiomes on Earth, continuously shaped by diverse microbial inputs and exposure to antimicrobial compounds and other stressors. These conditions may also harbor underexplored antimicrobial functions. Here we propose framing sludge as a dual-function node within AMR stewardship: a resource for routine surveillance and risk management, and a source material for an offline, containment-first workflow to identify antimicrobial candidates, particularly antimicrobial peptides. We summarize recent advances in metagenomics and machine-learning-enabled peptide prioritization and outline an evidence ladder that links sequence signals to functional validation. A central principle is to decouple discovery from plant operations and to apply explicit decision gates early in the pipeline, including cross-resistance screening and resistance-evolution assays, to prevent inadvertently increasing selection pressure or AMR risks. Finally, we call for shared benchmarks to improve comparability across studies, including curated datasets, standardized validation panels, and routine reporting of negative findings and resistance-related outcomes. Together, these steps can help translate sludge-enabled discovery into environmentally responsible innovation aligned with AMR stewardship.