ColV plasmids of extraintestinal pathogenic Escherichia coli (ExPEC) encode a variety of fitness and virulence factors and have long been associated with septicemia and avian colibacillosis. These plasmids are found significantly more often in ExPEC, including ExPEC associated with human neonatal meningitis and avian colibacillosis, than in commensal E. coli. Here we describe pAPEC-O103-ColBM, a hybrid RepFIIA/FIB plasmid harboring components of the ColV pathogenicity island and a multidrug resistance (MDR)-encoding island. This plasmid is mobilizable and confers the ability to cause septicemia in chickens, the ability to cause bacteremia resulting in meningitis in the rat model of human disease, and the ability to resist the killing effects of multiple antimicrobial agents and human serum. The results of a sequence analysis of this and other ColV plasmids supported previous findings which indicated that these plasmid types arose from a RepFIIA/FIB plasmid backbone on multiple occasions. Comparisons of pAPEC-O103-ColBM with other sequenced ColV and ColBM plasmids indicated that there is a core repertoire of virulence genes that might contribute to the ability of some ExPEC strains to cause high-level bacteremia and meningitis in a rat model. Examination of a neonatal meningitis E. coli (NMEC) population revealed that approximately 58% of the isolates examined harbored ColV-type plasmids and that 26% of these plasmids had genetic contents similar to that of pAPEC-O103-ColBM. The linkage of the ability to confer MDR and the ability contribute to multiple forms of human and animal disease on a single plasmid presents further challenges for preventing and treating ExPEC infections.ColV plasmids have a long history in scientific literature describing their association with the virulence of extraintestinal pathogenic Escherichia coli (ExPEC) (58). The first completed ColV plasmid sequence (24) localized the genes encoding the virulence traits to a 94-kb pathogenicity-associated island (PAI). Gene prevalence studies involving the genes in this PAI confirmed the hypothesis of Waters and Crosa that there are "constant" and "variable" portions of the ColV PAI and that the constant region contains the RepFIB and aerobactin operons (58). Since those studies, several more of these plasmids have been sequenced, including a plasmid variant known as ColBM, which is closely related to ColV plasmids, containing remnants of the ColV operon and the ColV PAI in a very similar arrangement (23). ColV and ColBM plasmids have been found to occur significantly more often in ExPEC than in commensal E. coli. Furthermore, recent work suggests that some ExPEC subpathotypes, including avian pathogenic E. coli (APEC) and human neonatal meningitis E. coli (NMEC), harbor these plasmids more often than other subpathotypes (10,24,26,35,42). Interestingly, although these plasmids are very prevalent in NMEC populations, the most-studied NMEC isolates appear to lack these plasmids (31, 61). Thus, far, it has been shown that ColV and ColBM plasmids co...