Abstract Description

Antimicrobial resistance (AMR) is a major global health concern that threatens the efficacy of interventions against infectious diseases. This is especially pertinent in Africa, where studies show rising infectious disease and AMR burden, partly driven by inadequate health and sanitation systems. While the overuse of antibiotics in clinical settings is a key driver of AMR, studies have also highlighted chemical contaminants and ecological changes as important contributors. These factors influence AMR distribution patterns, particularly in environmental hotspots such as wastewater treatment plants (WWTPs). However, these factors are often overlooked in current AMR risk assessments. Furthermore, the mechanisms mediating the active expression of antimicrobial resistance genes (ARGs) remain understudied. This is important because actively expressed ARGs pose a higher risk of treatment failure. This study aims to investigate the potential influence of ecological and physicochemical factors on ARG expression patterns across nine urban WWTPs and associated freshwater systems in South Africa. Using integrated metagenomic, metatranscriptomic and physicochemical analyses, this comprehensive approach will offer a mechanistic understanding of the factors sustaining AMR in WWTPs and associated freshwater environments. These findings will support the development of more effective public health and sanitation intervention strategies.