Project Summary/Abstract The increased prevalence of antimicrobial resistance (AMR) among Enterobacteriaceae has had major clinical and economic impacts in human medicine. Many of the multi-drug resistant (MDR) Enterobacteriaceae found in humans are community-acquired and linked to food-animals (i.e. livestock raised for meat and dairy products). The objective of this research project is to apply epidemiologic methods and next-generation DNA sequencing to quantify the exchange of MDR strains of E. coli and mobile genetic elements (e.g. plasmids, transposons, etc.) between food-animals and children living in peri-urban parishes east of Quito, Ecuador where small-scale food-animal production is widespread. The study will include households with young children in three neighborhood types: 1) neighborhoods with no food-animal production; 2) neighborhoods with small-scale food-animal production only; and 3) neighborhoods with small-scale and commercial-scale food- animal production. Approach: In Aim 1, we will examine whether young children and food-animals share E. coli clones [assessed by whole genome multi-locus sequence typing (wgMLST)] that also have the same phenotypic multi-drug resistance pattern. In Aim 2, we will identify MDR E. coli strains in young children and animals that are not clones (identified by wgMLST) but share the same phenotypic multi-drug resistance pattern. We will then analyze the mobile genetic elements associated with the observed phenotypic resistance patterns and characterize the phylogenetic relationship of the mobile genetic elements responsible for resistance gene transfer. In Aim 3a, we will examine whether food-animal production poses a significant risk for transmission of AMR to children, controlling for other known risk factors, and in Aim 3b, we will apply qualitative research methods to characterize the drivers of antimicrobial use in small-scale food-animal production. Expected Outcomes: To our knowledge, the proposed study will be one of the first of its kind and will likely set a precedent for future studies that aim to better understand community transmission of AMR. This study will likely make major contributions to our understanding of: i) mechanistic questions of AMR transmission (i.e. clonal spread versus horizontal gene transfer); ii) exposure-related questions of AMR transmission (i.e. risk factors associated with colonization with MDR/ESBL-E. coli); and iii) an understanding of the driving factors for use of antimicrobials in small-scale food-animal production.

Project Narrative The prevalence of multi-drug resistant (MDR) Enterobacteriaceae is increasing, and infections with these organisms are no longer limited to those associated with healthcare facilities. Many of the MDR Enterobacteriaceae found in humans are community-acquired and linked to food-animals (i.e. livestock raised for meat and dairy products). This study will apply next-generation DNA sequencing and epidemiologic methods to quantify the exchange of MDR strains of E. coli and mobile genetic elements (e.g., plasmids) between food-animals and children living in peri-urban communities east of Quito, Ecuador where small-scale food-animal production is widely practiced.