Bioactive environments to combat antimicrobial resistance: artificial intelligence and model-driven microbial...

Antimicrobial resistance (AMR) continues to outpace development of new therapeutics. Many interventions focus on treating infection after it occurs, but resistant pathogens often emerge, persist, and spread within reservoirs, such as built environments. Microbial biocontrol offers a complementary, upstream strategy by reshaping ecological interactions to suppress the colonization, persistence, and transmission of AMR pathogens. Currently, biocontrol design relies upon the presumed functionality of probiotic genera across diverse environments despite limited experimental validation, alongside heuristic model predictions that prioritize efficiency over sensitivity. These approaches yield inconsistent outcomes, reflecting the context-dependent nature of microbial behavior. We review how advances in metabolic modeling and artificial intelligence (AI), in conjunction with experimental data, enable adaptable, context-aware biocontrol design with iterative design-test-learn cycles for optimization. We outline the ecological principles underlying microbial competition, highlighting Bacillus as a robust biocontrol chassis due to its biosynthetic capacity, stress tolerance, and genetic tractability. We then discuss how genome-scale, pan-genome-scale, and metabolism-and-expression models provide mechanistic insight into competitive fitness, metabolic trade-offs, and persistence. AI advances these approaches by extracting patterns from multi-omic datasets to build specific, yet versatile, foundation models that guide strain and/or consortium selection for specific built environments. Moreover, these tools facilitate safe biocontrol deployment by enabling risk assessment of persistence, ecological displacement, and horizontal gene transfer, particularly for engineered living materials and bioactive building surfaces. Ultimately, AI-guided modeling and systems-level design provide scalable frameworks for developing durable, preventive strategies against AMR, shifting the focus from reactive treatment toward proactive control of pathogen ecology.