Host Colonization as a Major Evolutionary Force Favoring the Diversity and the Emergence of the Worldwide Multidrug-Resistant <italic toggle="yes">Escherichia coli</italic> ST131

ABSTRACT The emergence of multidrug-resistant Escherichia coli ST131 is a major worldwide public health problem in humans. According to the “one health” approach, this study investigated animal reservoirs of ST131, their relationships with human strains, and the genetic features associated with host colonization. High-quality genomes originating from human, avian, and canine hosts were classified on the basis of their accessory gene content using pangenomic. Pangenomic clusters and subclusters were specifically and significantly associated with hosts. The functions of clustering accessory genes were mainly enriched in functions involved in DNA acquisition, interactions, and virulence (e.g., pathogenesis, response to biotic stimulus and interaction between organisms). Accordingly, networks of cooccurrent host interaction factors were significantly associated with the pangenomic clusters and the originating hosts. The avian strains exhibited a specific content in virulence factors. Rarely found in humans, they corresponded to pathovars responsible for severe human infections. An emerging subcluster significantly associated with both human and canine hosts was evidenced. This ability to significantly colonize canine hosts in addition to humans was associated with a specific content in virulence factors (VFs) and metabolic functions encoded by a new pathogenicity island in ST131 and an improved fitness that is probably involved in its emergence. Overall, VF content, unlike the determinants of antimicrobial resistance, appeared as a key actor of bacterial host adaptation. The host dimension emerges as a major driver of genetic evolution that shapes ST131 genome, enhances its diversity, and favors its dissemination. IMPORTANCE Until now, there has been no indication that the evolutionary dynamics of Escherichia coli ST131 may reflect independent and host-specific adaptation of this lineage outside humans. In contrast, the limited number of ST131 reports in animals supported the common view that it rather reflects a spillover of the human sector. This study uncovered a link between host, ST131 population structure, and virulence factor content which appeared to reflect adaptation to hosts. This study helps to better understand the reservoir of ST131, the putative transmission flux, associated risks and the evolutionary dynamics of this bacterial population and highlights a paradigm in which host colonization stands as a key ecological force of the ST131 evolution.