|JOHNSON, TIMOTHY J - University Of Minnesota|
|SINGER, RANDALL S - University Of Minnesota|
|ISAACSON, RICHARD E - University Of Minnesota|
|DANZEISEN, JESSICA L - University Of Minnesota|
|LANG, KEVIN - University Of Minnesota|
|KOBLUK, KRISTI - University Of Minnesota|
|RIVERT, BERNADETTE - University Of Minnesota|
|BOREWICZ, KLAUDYNA - University Of Minnesota|
|ENGLEN, MARK D - Former ARS Employee|
|ANDERSON, JANET - University Of Minnesota|
|DAVIES, PETER - University Of Minnesota|
Submitted to: Applied and Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2015
Publication Date: 5/15/2015
Citation: Johnson, T., Singer, R., Isaacson, R., Danzeisen, J., Lang, K., Kobluk, K., Rivert, B., Borewicz, K., Frye, J.G., Englen, M., Anderson, J., Davies, P. 2015. In vivo transmission of an IncA/C plasmid in Escherichia coli depends on tetracycline concentration, and acquisition of the plasmid results in a variable cost of fitness. Applied and Environmental Microbiology. 81(10):3561-3570.
Interpretive Summary: Bacteria resistant to antimicrobials can result in infections that are difficult to treat. The genes that encode antimicrobial resistances are often located on plasmids, which are small genetic elements independent of the bacterial chromosome. These plasmids can be transferred between related and unrelated bacterial species resulting in antimicrobial resistance in new host bacteria. A class of plasmids known as IncA/C plasmids, which carry genes for multidrug resistances (MDR), have been found in bacteria isolated from humans and animals globally. The use of antibiotics is suspected to be causing the spread of MDR IncA/C plasmids and the emergence of MDR strains. However, few studies have determined the impact of different types of antibiotic administration on the selection of MDR plasmid-containing bacteria. This study sought to determine if two different levels of the antibiotic chlortetracycline treatment in pig feed had an impact on the prevalence and transmission of MDR IncA/C plasmids encoding chlortetracycline resistance. Low-dose administration of chlortetracycline to pigs had no impact on isolation of Escherichia coli containing MDR IncA/C plasmids from the pigs. High-dose administration resulted in increased isolation of E. coli containing MDR IncA/C plasmid from the pigs, and increased transfer of the MDR IncA/C plasmid to other intrinsic E. coli host bacteria in the pigs. There was no evidence of the MDR IncA/C plasmid being transferred to bacterial species other than E. coli in the pigs. Laboratory (In vitro) transfer and selection experiments demonstrated that high-dose levels of chlortetracycline enhanced MDR IncA/C plasmid transfer, while low-dose concentrations selected for MDR IncA/C plasmid-containing E. coli. These results improve our understanding of the effects of low and high level antibiotic treatment in animals and reveal some of the mechanisms likely leading to this difference.
Technical Abstract: IncA/C plasmids are broad-host-range plasmids enabling multidrug resistance that have emerged worldwide among bacterial pathogens of humans and animals. While antibiotic usage is suspected to be a driving force in the emergence of such strains, few studies have examined the impact of different types of antibiotic administration on the selection of plasmid-containing multidrug resistant isolates. We sought to determine if two different levels of chlortetracycline treatment in pig feed had an impact on the prevalence and dissemination of IncA/C plasmids. Continuous low-dose administration of chlortetracycline had no observable impact on proportions of IncA/C plasmid-containing E. coli from pig feces over the course of 35 days. In contrast, high-dose administration of chlortetracycline resulted in increased proportions of IncA/C plasmid-containing E. coli in pig feces, and increased movement of the IncA/C plasmid to other indigenous E. coli hosts. There was no evidence of conjugal transfer of the IncA/C plasmid to bacterial species outside of E. coli. In vitro competition assays demonstrated that bacterial host background substantially impacts the cost of IncA/C plasmid carriage in E. coli and Salmonella. Fitness cost was the smallest for E. coli belonging to phylogenetic group A and for Salmonella belonging to the Typhimurium serotypes. In vitro transfer and selection experiments demonstrated that higher levels of tetracycline enhanced IncA/C plasmid conjugative transfer, while low-dose concentrations of tetracycline selected for IncA/C plasmid-containing E. coli. Together, these experiments improve our knowledge on the impact of differing concentrations of tetracycline on the selection of IncA/C-type plasmids.