Chlortetracycline enhances tonsil colonization and fecal shedding of multidrug-resistant Salmonella enterica serovar Typhimurium DT104 without Major Alterations to the Porcine Tonsillar and Intestinal Microbiota

Authors: HOLMAN, DEVIN - Orise Fellow; Bearson, Bradley - Brad; Allen, Heather; Shippy, Daniel; Loving, Crystal; Kerr, Brian; Bearson, Shawn; Brunelle, Brian

Submitted to: Applied and Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2018
Publication Date: 12/7/2018
Citation: Holman, D., Bearson, B.L., Allen, H.K., Shippy, D.C., Loving, C.L., Kerr, B.J., Bearson, S.M., Brunelle, B.W. 2018. Chlortetracycline enhances tonsil colonization and fecal shedding of multidrug-resistant Salmonella enterica serovar Typhimurium DT104 without major alterations to the porcine tonsillar and intestinal microbiota. Applied and Environmental Microbiology. 85(4):e02354-18. https://doi.org/10.1128/AEM.02354-18.
DOI: https://doi.org/10.1128/AEM.02354-18

Interpretive Summary: Salmonella is an important cause of foodborne illness in North America, and pork products are associated with sporadic cases and outbreaks of human salmonellosis. Isolates of Salmonella may be resistant to multiple antibiotics, and infections with multidrug-resistant Salmonella are more difficult to treat, leading to increased hospitalization rates. Swine operations commonly use antimicrobials such as chlortetracycline to prevent and treat non-Salmonella infections, which may have collateral effects on other bacterial populations in the pig. In our current study, we show increased tonsillar colonization and fecal shedding of a multidrug-resistant strain of Salmonella enterica serovar Typhimurium from pigs administered chlortetracycline, despite the pig gut bacteria remaining relatively stable throughout the experiment. Therefore, in a production setting, pigs unknowingly colonized with multidrug-resistant Salmonella receiving chlortetracycline for an unrelated disease may be at a greater risk for disseminating multidrug-resistant Salmonella to other pigs and to humans through environmental or pork product contamination.

Technical Abstract: Salmonella is a frequent cause of human foodborne illness, and pigs can often be colonized with Salmonella asymptomatically. Multidrug-resistance is widespread among Salmonella enterica serovar Typhimurium (S. Typhimurium) isolates, and multidrug resistant (MDR) strains are associated with an increased rate of hospitalization and other complications. Chlortetracycline is commonly used in swine production to prevent and treat various diseases; therefore, chlortetracycline treatment of pigs unknowingly colonized with MDR Salmonella may have collateral effects on Salmonella (and other gut bacteria). In this study, we determined the effect of in-feed chlortetracycline at a therapeutic regimen of 400 g/ton on shedding and colonization of pigs challenged with an MDR S. Typhimurium DT104 strain. We also assessed the impact on the fecal microbiota over the 12-day experimental period as well as the ileum, cecum, and tonsil microbiota at 7 days post-inoculation (dpi). In MDR S. Typhimurium-inoculated pigs, chlortetracycline administration significantly increased fecal shedding at 2 dpi and enhanced tonsil colonization (P less than 0.001). Although few major alterations were detected in the gut microbiota of pigs treated with MDR S. Typhimurium and/or chlortetracycline, the largest effect for both was on the structure of the ileal mucosal and tonsillar microbiota. Microbial richness (number of OTUs) was reduced by both chlortetracycline and MDR S. Typhimurium in the ileal and cecal mucosa (P less than 0.05). The transcriptome of the tonsils was largely unaffected despite increased colonization by MDR S. Typhimurium in the chlortetracycline-treated pigs. These results highlight that chlortetracycline administration can enhance shedding and colonization of MDR S. Typhimurium in pigs, which could increase the risk of environmental dissemination of MDR Salmonella strains.