Chlortetracycline Enhances Tonsil Colonization and Fecal Shedding of Multidrug-Resistant Serovar Typhimurium DT104 without Major Alterations to the Porcine Tonsillar and Intestinal Microbiota.

spp. are estimated to cause 1.2 million cases of human foodborne illness each year in the United States, and pigs can often be asymptomatically colonized with spp. (>50% of farms). Recent reports state that 18.3% of serovar Typhimurium isolates are resistant to ≥3 antimicrobial classes, and multidrug-resistant (MDR) strains are associated with an increased hospitalization rate and other complications. Chlortetracycline is commonly used in swine production to prevent/treat various diseases; therefore, chlortetracycline treatment of pigs unknowingly colonized with MDR may have collateral effects on spp. (and other gut bacteria). In this study, we determined the effect of in-feed chlortetracycline (400 g/ton) on shedding and colonization of pigs challenged with the MDR Typhimurium strain DT104 ( = 11/group). We also assessed the impact on the fecal microbiota over the 12-day experimental period and on the ileum, cecum, and tonsil microbiota at 7 days postinoculation (dpi). In MDR Typhimurium-inoculated pigs, chlortetracycline administration significantly increased fecal shedding at 2 dpi (+1.4 log CFU/g;  < 0.001) and enhanced tonsil colonization (+3.1 log CFU/g;  < 0.001). There were few major alterations detected in the gut or tonsillar microbiota of pigs treated with MDR Typhimurium and/or chlortetracycline. The tonsillar transcriptome was largely unaffected despite increased colonization by MDR Typhimurium following inoculation of the chlortetracycline-treated pigs. These results highlight the idea that chlortetracycline administration can enhance shedding and colonization of MDR Typhimurium in pigs, which could increase the risk of environmental dissemination of MDR strains. spp. are an important cause of foodborne illness in North America, and pork products are associated with sporadic cases and outbreaks of human salmonellosis. Isolates of may be resistant to multiple antibiotics, and infections with multidrug-resistant (MDR) spp. are more difficult to treat, leading to increased hospitalization rates. Swine operations commonly use antimicrobials, such as chlortetracycline, to prevent/treat infections, which may have collateral effects on pig microbial populations. Recently, we demonstrated that chlortetracycline induces the expression of genes associated with pathogenesis and invasion in MDR serovar Typhimurium In our current study, we show increased tonsillar colonization and fecal shedding of the MDR Typhimurium strain DT104 from pigs administered chlortetracycline. Therefore, pigs unknowingly colonized with multidrug-resistant spp. and receiving chlortetracycline for an unrelated infection may be at a greater risk for disseminating MDR spp. to other pigs and to humans through environmental or pork product contamination.