PROJECT SUMMARY Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections (UTIs) globally, resulting in enormous health and social costs. In the past decade, research has shown that UPEC strains are not just transmitted person-to-person; environmental sources, such as food-animal products, also contribute to transmission. Applying comparative genomics, we have identified host-associated mobile genetic elements (MGEs) that can be used to identify the vertebrate host from which a strain originates. Applying these methods in the United States, we have found that approximately 8% of human UTIs can be linked directly to UPEC from meat and poultry products. In low- and middle-income countries (LMICs), the intensity of human-animal interactions is greater suggesting a different ecology for UPEC transmission. A literature review by our team demonstrates that UPEC transmission is poorly understood in LMICs. In this study, we will integrate comparative genomics, exposure assessment and spatiotemporal analyses to determine the drivers of UPEC epidemiology in poor, marginalized communities of an LMIC. We will leverage over 20 years of experience working in northwestern coastal Ecuador, a region that has been historically neglected in the context of health infrastructure and where communities live in proximity with livestock, poultry, and pets. We have developed a research platform studying diarrheal and vectorborne diseases, and have fully developed survey instruments to capture demographic, socioeconomic, and water, sanitation and hygiene data, and fully developed assays to process blood and stool samples. Our goals for this project are to identify the dominant zoonotic sources of UPEC, quantify the transmission to humans and characterize the behaviors and environmental conditions associated with risk for colonization and infection. We will carry out active surveillance at regional hospitals over a 30-month period and follow 420 households prospectively over a 4- year period. We hypothesize that domestic animal species will be important sources of UPEC within LMIC settings like our study site and will be major drivers for UPEC colonization. The study will characterize the role that domestic animals play in the transmission of UPEC in an LMIC setting, where environmental transmission pathways are likely much more important compared to high-income settings. By identifying specific reservoirs of UPEC and high-risk exposures, we will define optimal mitigation strategies to decrease disease burden in resource poor settings. Understanding how host-specific genetic markers vary in an LMIC is important for developing targets of diagnostics and therapeutic interventions.

PROJECT NARRATIVE Uropathogenic E. coli (UPEC) are the main etiologic agent of urinary tract infections in humans that result in enormous health and social costs across the globe. There is now evidence that UPEC strains routinely colonize food animals serving as a likely link between food-animal E. coli and human UTIs. This longitudinal study will define domestic animal host features of UPEC and model human exposures to uropathogenic E. coli (UPEC) in poor communities of Northwest Ecuador to understand the drivers of exposure to UPEC among households.