The main aim of this research project is to determine the prevalence of, characterize, and track antimicrobial resistance (AR) in the water-plant-food-public health interface. This will contribute to addressing the knowledge gap on the contribution of agro-ecosystems to the dissemination of AR resistance in the environment in South Africa. Access to safe potable water is a basic human right. The microbiological quality of water sources, especially surface water, are seriously compromised by municipal wastewater discharge, sewage from informal settlements with inadequate sanitation, and wastes from animal husbandry, industrial companies, hospitals, and the mining sector. With strategic resources being polluted, consumers face increased risks with potential negative effects on human health, the environment, and food security. Following consultation with key stakeholders, the research team will select study sites where the risk for fecal bacterial contamination is high due to anthropogenic activities. They will compare levels of antimicrobial resistance prevalence in rural versus urban settings and organic farming versus intensive commercial farming, which should contribute towards an improved understanding of the role of agricultural practices on driving AR development in the agricultural ecosystem.