Genomic epidemiology reveals statewide dispersal of clinical Shiga toxin-producing <i>Escherichia coli</i> and their antimicrobial resistome

Shiga toxin-producing <i>Escherichia coli</i> (STEC) is a zoonotic pathogen that can be transmitted to humans through contaminated food or contact with infected animals. Here, we aim to characterize the population diversity and genome characteristics of the clinical STEC population in New York State collected over a span of six years. A total of 1,655 clinical isolates were analyzed using whole-genome sequencing, phylogenetic reconstruction, <i>in silico</i> identification of acquired antimicrobial resistance genes and plasmid types, and delineation of genetic clusters. The STEC population consists of 178 serotypes based on unique combinations of the O and H antigens. Four serotypes were most frequently detected: O103:H2 (<i>n</i> = 295 genomes), O157:H7 (<i>n</i> = 207), O26:H11 (<i>n</i> = 137), and O111:H8 (<i>n</i> = 126). The accessory genome content of O157:H7 was more divergent from those of other three serotypes. A total of 93 genetic determinants associated with resistance to 13 classes of antimicrobial agents were identified. Across the whole data set, we detected 10 subtypes of the Shiga toxin gene <i>stx</i>. The gene encoding intimin (<i>eae</i>) was present in 70.39% of the genomes. Of the 56 plasmid replicon types detected, the most abundant was IncFIB(AP001918). Using a cutoff of 10 SNPs in the core gene alignment, we identified 28 genetic clusters implicating at least ten serotypes. O157:H7 genomes were identified in eight clusters. These genetically linked cases, spanning anywhere between 1 day and 63 months and traversing multiple counties across the state, suggest either cryptic outbreaks or long-term local persistence.IMPORTANCEShiga toxin-producing <i>Escherichia coli</i> (STEC) infections are a major public health burden. We show that while serotypes O103:H2 and O157:H7 remain the major causes of STEC infections in New York State, the rising incidence of less common serotypes is a cause of concern, especially given the large pool of AMR, virulence genes, and plasmids they carry. Genomic surveillance of STEC is critical in informing public health efforts to reduce the burden of multidrug-resistant STEC, minimize onward transmission, and prevent more severe disease outcomes.