Global Footprint of the Multidrug Resistance Island Ec17R and Resistance Gene Co-Occurrence in Clinical Escherichia coli Isolates Supplemental Tables

Multidrug resistant (MDR) bacterial pathogens are a major threat to global health, limiting treatment options for common infections. Extraintestinal Pathogenic Escherichia coli (ExPEC), a leading cause of bloodstream and urinary tract infections (UTIs), are often resistant to one or more antibiotic classes. Previously, we identified a clonal group of ExPEC strains (P1A) that persisted over a 5-year period from 2012 to 2016 within an elderly woman who suffered from frequent recurrent UTIs. A subset of these isolates carried a plasmid-borne MDR island (Ec17R) harboring 17 resistance genes. Sampling of fecal and urine samples in 2019 indicated that the patient remained colonized with the P1A lineage, including Ec17R-positive strains, over 7 years after collection of the first P1A isolates in 2012. Using comparative genomics, we show that the Ec17R island is globally distributed across diverse bacterial species from various environmental, agricultural, and clinical sources, highlighting the broad mobility and public health relevance of Ec17R. Notably, Ec17R also links the longitudinal rUTI case with a broader patient-derived ExPEC population, where we identified ten additional isolates carrying Ec17R or highly similar MDR islands. By applying clustering approaches and Bayesian network modeling to 267 isolates from pediatric patients with invasive ExPEC infections, we found that functionally distinct classes of resistance genes (including several heavy metal resistance genes) have a high probability of co-occurrence, possibly reflecting carriage within MDR islands like Ec17R. Finally, we observed that strains within the P1A lineage are recalcitrant to antibiotics for which they have no known resistance mechanisms, suggesting that these pathogens have means beyond their formidable array of resistance genes to survive within a host for years despite the administration of numerous, robust antimicrobial treatments.