Molecular epidemiology of the multidrug-resistant Escherichia coli sequence type 131-H30 lineage among U.S. children

Abstract

Escherichia coli sequence type 131-H30 is a globally important pathogen implicated in rising rates of antimicrobial resistance among extraintestinal E. coli infections. H30 causes both community- and healthcare-associated infections, and is associated with resistance to several commonly used antimicrobial agents. This dissertation addresses several knowledge gaps about the epidemiology and transmission dynamics of H30 among U.S. children through the integration of high-resolution molecular data from clinical extraintestinal E. coli isolates with patient epidemiologic data. I observed that although H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, it is similarly dominant among very antimicrobial-resistant isolates. Additionally, H30 is especially dominant among young children when compared to other types of antimicrobial-resistant extraintestinal E. coli. Whole genome sequencing analyses provided proof of principle that putative transmission clusters of H30 can be identified from passively collected clinical isolates. Integration of data describing patient healthcare contact into a temporal phylogenomic analysis revealed that ancestral H30 isolates were more likely to be community-associated than healthcare-associated. Finally, when evaluating the evolutionary dynamics of resistance to trimethoprim-sulfamethoxazole, a commonly used antimicrobial agent in pediatrics, I found that the acquisition of resistance to this agent likely occurred prior to the differentiation of specific H30 subtypes. Together, these findings highlight that high-resolution molecular analyses of isolates collected during routine clinical care, when combined with patient data, can offer valuable insights into resistance and transmission dynamics of concerning antimicrobial-resistant pathogens like H30.