The phylogenetic distributions of multiple putative virulence factors (VFs) and papA (P fimbrial structural subunit) alleles among 182 Escherichia coli blood isolates from patients with diverse-source bacteremia were defined. Phylogenetic correspondence among these strains, the E. coli Reference (ECOR) collection, and other collections of extraintestinal pathogenic E. coli (ExPEC) was assessed. Although among the 182 bacteremia isolates phylogenetic group B2 predominated, exhibited the greatest concentration of individual VFs, and contained the largest number of familiar virulent clones, other phylogenetic groups exhibited greater concentrations of certain VFs than did group B2 and included several additional virulent clones. Certain of the newly detected VF genes, e.g., fyuA (yersiniabactin; 76%) and focG (F1C fimbriae; 25%), were as prevalent or more prevalent than their more familiar traditional counterparts, e.g., iut (aerobactin; 57%) and sfaS (S fimbriae; 14%), thus possibly offering additional useful targets for preventive interventions. Considerable diversity of VF profiles was observed at every level within the phylogenetic tree, including even within individual lineages. This suggested that many different pathways can lead to extraintestinal virulence in E. coli and that the evolution of ExPEC, which involves extensive horizontal transmission of VFs and continuous remodeling of pathogenicityassociated islands, is a highly active, ongoing process.The strains of Escherichia coli that cause extraintestinal infections such as urinary tract infection (UTI), meningitis, and bacteremia are distinct both from most intestinal commensal E. coli types and from diarrheagenic E. coli types (13,57,65,70). These specialized extraintestinal pathogenic E. coli (ExPEC) strains (65) are thought to derive primarily from E. coli phylogenetic group B2 (as defined within the E. coli Reference [ECOR] collection by multilocus enzyme electrophoresis [MLEE]) (20,54) and to acquire their unique pathogenicity from their distinctive virulence factors (VFs) (4,10,59,60).Putative VFs of ExPEC include diverse adhesins, toxins, polysaccharide coatings (including capsules and lipopolysaccharides), siderophores, serum resistance mechanisms, and invasins (21,33,70). Such VFs help the organisms colonize host surfaces, avoid and/or subvert host defense mechanisms, injure and/or invade host cells and tissues, and incite a noxious inflammatory response, thereby giving rise to clinical disease (12, 21, 70). The VF genes of ExPEC are thought to be primarily inherited vertically within evolutionary lineages but also to be transferred horizontally between lineages, in some instances on plasmids or on "pathogenicity-associated islands" (PAIs), which are gene blocks that contain multiple contiguous VF genes (2,10,16,18,36,50,61). Better understandings of the prevalence and evolutionary origins of the VFs of ExPEC and of the distinctive "virulent clones" that make up the ExPEC population should hasten the development of the preventive measures that...