Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 23, 2014
Publication Date: February 11, 2014
Citation: Bearson, B.L., Allen, H.K., Brunelle, B.W., Lee, I.S., Casjens, S.R., Stanton, T.B. 2014. The agricultural antibiotic carbadox induces phage-mediated gene transfer in Salmonella. Frontiers in Microbiology. 5:1-8. Interpretive Summary: Antibiotics are used in human and animal medicine to prevent and treat illness due to disease-causing bacteria. However, exposure to antibiotics can lead to antibiotic resistance development in both beneficial and disease-causing bacteria, making future treatment with antibiotics less effective. Additionally, bacteria further complicate the problem by transferring genes among themselves, and one mechanism of gene transfer is viruses of bacteria (bacteriophages). We determined the role of bacteriophages in the transfer of antibiotic resistance and virulence genes among isolates of the foodborne pathogen Salmonella. We also tested the antibiotic carbadox for its ability to activate bacteriophages that are present within the bacterial cell. This study demonstrates that carbadox can activate viruses in the foodborne pathogen Salmonella. The viruses activated by carbadox in the donor Salmonella strain can transfer Deoxyribonucleic acid (DNA) into a new recipient Salmonella strain. The transfer of DNA into the new strain may provide growth advantages to the recipient strain by providing virulence or antibiotic resistance genes. Virus transfer of DNA between bacterial strains due to carbadox activation may contribute to bacterial strain evolution. The results benefit scientists who are developing ways to mitigate the antibiotic resistance problem in bacteria.
Technical Abstract: Antibiotics are used for their disease therapeutic or preventative effects in humans and animals, as well as for enhanced feed conversion efficiency in livestock. Antibiotics can also cause undesirable effects in microbial populations, including selection for antibiotic resistance, enhanced pathogen invasion, and stimulation of horizontal gene transfer. Carbadox is a veterinary antibiotic used in the U.S. during the starter phase of swine production for improved feed efficiency and control of swine dysentery and bacterial swine enteritis. Carbadox has been shown in vitro to induce phage-encoded Shiga toxin in Shiga toxin-producing Escherichia coli and antibiotic resistance gene transfer mediated by a phage-like element in Brachyspira hyodysenteriae, but the effect of carbadox on prophages in other bacteria is unknown. This study examined carbadox exposure on prophage induction and genetic transfer in Salmonella enterica serovar Typhimurium, a human foodborne pathogen that frequently colonizes swine without causing disease. S. Typhimurium LT2 exposed to carbadox induced prophage production, resulted in bacterial cell lysis and visible virions by electron microscopy. Carbadox induction of phage-mediated gene transfer was confirmed by monitoring the transduction of a sodCIII::neo cassette in the Fels-1 prophage from LT2 to a recipient Salmonella strain. Furthermore, carbadox frequently induced generalized transducing phages in multidrug-resistant phage-type DT104 and DT120 isolates, resulting in the transfer of chromosomal and plasmid DNA that included antibiotic resistance genes. Our research indicates that exposure of Salmonella to carbadox induces prophages that can transfer virulence and antibiotic resistance genes to susceptible bacterial hosts. Carbadox-induced, phage-mediated gene transfer could serve as a contributing factor in bacterial evolution during animal production, with phages being a reservoir for bacterial fitness genes in the environment.