Public health risk and environmental factors associated with the presence of clinically relevant antimicrobial resistant Enterobacterales in rivers in central Chile

FONDECYT 1221536

The overuse of antibiotics has led to the widespread emergence of antimicrobial resistance (AMR), posing a significant threat to public health. The WHO predicted that AMR bacteria would cause approximately 10 million deaths annually and cost about USD100 trillion by 2050 if no new interventions were developed. Studies suggest that freshwater systems represent key sources and pathways for the environmental transmission of clinically relevant AMR Enterobacteria (e.g., cephalosporin-resistant E. coli or Klebsiella pneumoniae) between agricultural, natural, and urban environments, particularly in low-income communities. However, the ecology and processes underpinning clinically relevant AMR Enterobacterales transmission in freshwater systems are poorly understood, limiting efforts to identify effective strategies for monitoring and mitigating AMR. Informal settlements (slums) are at greater risk for becoming hotspots of AMR bacteria and transmission, given their unique structural characteristics. These characteristics include high density of human, vermin, and animal populations, misuse of antibiotics, inadequate water and sanitation infrastructure, and limited access to essential services. Environmental conditions in slums, particularly when they are next to freshwater systems, may encourage the proliferation and transmission of resistant bacteria, posing a public health risk to slum dwellers and society at large. Although previous research has examined environmental factors associated with fecal pathogen contamination, little is known about the associations between multiple, concomitantly collected environmental (e.g., weather, physicochemical water quality) and anthropogenic (e.g., land use, living conditions) factors, and the likelihood of detecting specific clinically relevant AMR Enterobacterales. Factors associated with fecal pathogen detection vary within and between geographic regions and environmental risk factors, but we know little about risk factors connecting freshwater systems, agricultural, and human communities. We will direct our attention to clinically relevant AMR Enterobacterales (emphasizing carbapenem-resistant [CR] and extended-spectrum β-lactamase [ESBL] producing organisms) considered WHO priority pathogens. We hypothesize that clinically relevant AMR Enterobacterales isolated in the rivers and irrigation canals are genetically related (i.e., same clones and similar AMR pattern) to resistant Enterobacterales isolates from human hospitals and informal urban settlements, with environmental factors and their interactions, as indicators of the likelihood of detection of these isolates in the Maipo and Mapocho rivers and adjacent irrigation canals. We aim to test this hypothesis by identifying factors associated with AMR detection in two Chilean river systems and adjacent human communities. The specific study aims are:

• Specific Objective (SO) 1: Sample along irrigation canals the Mapocho and Maipo watersheds and collect environmental risk factors data (e.g., land use, potential sources of fecal contaminants, and AMR)

• SO2: Develop a rich, integrative dataset on individual and contextual characteristics from a sample of dwellers in informal urban settlements located next to the Mapocho and Maipo watersheds, including human fecal samples, environmental risk factors, and sociodemographic data

• SO3: Characterize patterns of antimicrobial resistance in Enterobacterales collected in water and slum dwellers (from SO1 and SO2), and clinical isolates from the Chilean Hospital network

• SO4: Determine the public health relevance of strains collected and characterized in SO1-SO3, comparing their genome sequences, and identifying whether they are the same bacteria or clone across locations.

• SO5: Determine the association between the environmental factors and the presence of clinically relevant antimicrobial resistance in Enterobacterales isolated in SO1 and SO2.

Our proposal considers a multidisciplinary one-health approach to tackle AMR by simultaneously identifying multiple environmental factors and their role as indicators on the presence of clinically relevant AMR Enterobacterales within two river systems in Central Chile and low-income communities. Specific sets of environmental conditions associated with an increased likelihood of AMR detection could be used as sentinel scenarios to identify when and where clinically relevant AMR Enterobacterales are likely to be present in Chilean surface water and identify effective AMR prevention and control strategies. We will evaluate the public health risk posed by AMR bacteria in the study region by comparing the AMR bacteria isolated as part of the proposed study with slum and clinical isolates using genomics methodology (clones and AMR profile). Our project results are critical to public health and food safety; information could be used to develop targeted AMR management strategies to reduce AMR pollution in surface water.