Interconnected reservoirs and escalating resistance in multidrug-resistant Pseudomonas aeruginosa: An One Health review.

Multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) has emerged as a major global health threat due to its intrinsic resistance mechanisms, remarkable genetic adaptability, and ability to persist across interconnected human, animal, food, and environmental reservoirs. Increasing evidence indicates that antimicrobial resistance (AMR) in P. aeruginosa is not confined to clinical settings but is sustained through complex ecological interactions involving wastewater systems, agricultural environments, aquaculture, food production chains, and the built environment. This narrative review synthesises current evidence on the emergence, molecular mechanisms, environmental reservoirs, and cross-sectoral transmission pathways of MDR P. aeruginosa within the One Health framework. The review further examines therapeutic challenges associated with intrinsic resistance, horizontally acquired resistance genes, adaptive tolerance mechanisms, and biofilm-mediated persistence. Emerging treatment strategies, including bacteriophage therapy, antimicrobial peptides, nanotechnology-based approaches, and predictive modelling for optimised antibiotic use, are also discussed. The findings highlight the convergence of resistance determinants across sectors and emphasize the role of environmental and anthropogenic drivers in sustaining AMR. Addressing MDR P. aeruginosa therefore requires integrated One Health strategies that combine antimicrobial stewardship, improved environmental management, strengthened surveillance systems, and responsible antimicrobial use across healthcare, agriculture, and environmental sectors. Coordinated interdisciplinary efforts will be essential to mitigate the growing global burden of MDR P. aeruginosa and preserve the effectiveness of current and future antimicrobial therapies.