RT Journal A1 Arimizu, Yoko A1 Kirino, Yumi A1 Sato, Mitsuhiko P. A1 Uno, Koichi A1 Sato, Toshio A1 Gotoh, Yasuhiro A1 Auvray, Frédéric A1 Brugere, Hubert A1 Oswald, Eric A1 Mainil, Jacques G. A1 Anklam, Kelly S. A1 Döpfer, Dörte A1 Yoshino, Shuji A1 Ooka, Tadasuke A1 Tanizawa, Yasuhiro A1 Nakamura, Yasukazu A1 Iguchi, Atsushi A1 Morita-Ishihara, Tomoko A1 Ohnishi, Makoto A1 Akashi, Koichi A1 Hayashi, Tetsuya A1 Ogura, Yoshitoshi T1 Large-scale genome analysis of bovine commensal Escherichia coli reveals that bovine-adapted E. coli lineages are serving as evolutionary sources of the emergence of human intestinal pathogenic strains JF Genome Research JO Genome Research YR 2019 FD September 01 VO 29 IS 9 SP 1495 OP 1505 DO 10.1101/gr.249268.119 UL http://genome.cshlp.org/content/29/9/1495.abstract AB How pathogens evolve their virulence to humans in nature is a scientific issue of great medical and biological importance. Shiga toxin (Stx)–producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are the major foodborne pathogens that can cause hemolytic uremic syndrome and infantile diarrhea, respectively. The locus of enterocyte effacement (LEE)–encoded type 3 secretion system (T3SS) is the major virulence determinant of EPEC and is also possessed by major STEC lineages. Cattle are thought to be the primary reservoir of STEC and EPEC. However, genome sequences of bovine commensal E. coli are limited, and the emerging process of STEC and EPEC is largely unknown. Here, we performed a large-scale genomic comparison of bovine commensal E. coli with human commensal and clinical strains, including EPEC and STEC, at a global level. The analyses identified two distinct lineages, in which bovine and human commensal strains are enriched, respectively, and revealed that STEC and EPEC strains have emerged in multiple sublineages of the bovine-associated lineage. In addition to the bovine-associated lineage-specific genes, including fimbriae, capsule, and nutrition utilization genes, specific virulence gene communities have been accumulated in stx- and LEE-positive strains, respectively, with notable overlaps of community members. Functional associations of these genes probably confer benefits to these E. coli strains in inhabiting and/or adapting to the bovine intestinal environment and drive their evolution to highly virulent human pathogens under the bovine-adapted genetic background. Our data highlight the importance of large-scale genome sequencing of animal strains in the studies of zoonotic pathogens.