In this study, a 101-kb IncF plasmid from an avian pathogenic Escherichia coli (APEC) strain (APEC O2) was sequenced and analyzed, providing the first completed APEC plasmid sequence. This plasmid, pAPEC-O2-R, has functional transfer and antimicrobial resistance-encoding regions. The resistance-encoding region encodes resistance to eight groups of antimicrobial agents, including silver and other heavy metals, quaternary ammonium compounds, tetracycline, sulfonamides, aminoglycosides, trimethoprim, and beta-lactam antimicrobial agents. This region of the plasmid is unique among previously described IncF plasmids in that it possesses a class 1 integron that harbors three gene cassettes and a heavy metal resistance operon. This region spans 33 kb and is flanked by the RepFII plasmid replicon and an assortment of plasmid maintenance genes. pAPEC-O2-R also contains a 32-kb transfer region that is nearly identical to that found in the E. coli F plasmid, rendering it transferable by conjugation to plasmid-less strains of bacteria, including an APEC strain, a fecal E. coli strain from an apparently healthy bird, a Salmonella enterica serovar Typhimurium strain, and a uropathogenic E. coli strain from humans. Differences in the G؉C contents of individual open reading frames suggest that various regions of pAPEC-O2-R had dissimilar origins. The presence of pAPEC-O2-R-like plasmids that encode resistance to multiple antimicrobial agents and that are readily transmissible from APEC to other bacteria suggests the possibility that such plasmids may serve as a reservoir of resistance genes for other bacteria of animal and human health significance.Antimicrobial resistance among bacterial pathogens of food animals can complicate veterinary therapy. Resistant animal pathogens may also be a threat to human health if these resistant bacteria enter the food supply or otherwise serve as reservoirs of resistance genes for human pathogens. Transmissible R plasmids that encode multidrug resistance would seem a likely means by which animal pathogens could acquire resistance genes or transmit them to human pathogens. This study examines an R plasmid encoding multidrug resistance in an avian pathogenic Escherichia coli (APEC) isolate. APEC strains are important and prevalent bacterial pathogens of poultry (3) and are frequently found to be resistant to multiple antimicrobial agents (21, 37), including ampicillin, tetracycline, aminoglycosides, fluoroquinolones, quaternary ammonium compounds, and heavy metals (37). Genes encoding such resistance are often found on large, transmissible R plasmids (20). Not surprisingly, multidrug-resistant APEC strains often carry conjugative plasmids (8). Interestingly, plasmids have been shown to be transferable from poultry to human isolates (23), suggesting that APEC strains and their plasmids might serve as reservoirs of resistance genes for bacteria that affect public health. In the present study, the first complete sequence of a transmissible APEC R plasmid is presented and analyzed. Additionally, an...