Chlortetracycline and florfenicol induce expression of genes associated with pathogenicity in multidrug-resistant Salmonella enterica serovar Typhimurium

Authors: HOLMAN, DEVIN - Orise Fellow; Bearson, Shawn; Bearson, Bradley - Brad; Brunelle, Brian

Submitted to: Gut Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/5/2018
Publication Date: 3/5/2018
Citation: Holman, D., Bearson, S.M., Bearson, B.L., Brunelle, B.W. 2018. Chlortetracycline and florfenicol induce expression of genes associated with pathogenicity in multidrug-resistant Salmonella enterica serovar Typhimurium. Gut Pathogens. 10:10. https://doi.org/10.1186/s13099-018-0236-y.
DOI: https://doi.org/10.1186/s13099-018-0236-y

Interpretive Summary: Various Salmonella serotypes cause foodborne illness in humans but can colonize livestock and poultry without causing clinical symptoms. Salmonella isolated from these food animals are frequently multidrug-resistant (MDR; resistant to greater than three or more antimicrobial classes). Chlortetracycline and florfenicol are antibiotics that are commonly used in veterinary medicine for respiratory and gastrointestinal infections. The concentrations used of chlortetracycline or florfenicol to clear these infections are considered to be sub-inhibitory to MDR Salmonella isolates. In this study, we exposed MDR Salmonella isolates to sub-inhibitory concentrations of either antibiotic and revealed that over 50 percent of the genes in the genome changed their expression levels, including genes involved in the ability of Salmonella to move (motility) and invade host cells (invasion). This suggests that antibiotic treatment of animals that are unknowingly colonized with MDR S. Typhimurium may enhance expression of Salmonella genes involved in pathogenicity, potentially prolonging host colonization and fecal shedding of this human foodborne pathogen. Knowledge of the antibiotics that enhance MDR Salmonella virulence mechanisms will provide information to aid in limiting the negative consequences of antibiotic therapy by allowing veterinarians to make informed decisions when determining antibiotic treatment for other bacterial infections.

Technical Abstract: Background Multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Typhimurium) is a serious public health threat as infections caused by these strains are more difficult and expensive to treat. Livestock serve as a reservoir for MDR Salmonella, and the antibiotics chlortetracycline and florfenicol are frequently administrated to food producing animals to treat and prevent various diseases. Therefore, we evaluated the response of MDR S. Typhimurium after exposure to these two antibiotics. Results We exposed four MDR S. Typhimurium isolates to sub-inhibitory concentrations of chlortetracycline (16 and 32 mu g/ml) or florfenicol (16 mu g/ml) for 30 min during early-log phase. Differentially expressed genes following antibiotic treatment were identified using RNA-seq, and genes associated with attachment and those located within the Salmonella pathogenicity islands were significantly up-regulated following exposure to either antibiotic. The effect of antibiotic exposure on cellular invasion and motility was also assessed. Swimming and swarming motility were decreased due to antibiotic exposure. However, we observed chlortetracycline enhanced cellular invasion in two strains and florfenicol enhanced invasion in a third isolate. Conclusions Chlortetracycline and florfenicol exposure during early-log growth altered the expression of nearly half of the genes in the S. Typhimurium genome, including a large number of genes associated with virulence and pathogenesis; this transcriptional alteration was not due to the SOS response. The results suggest that exposure to either of these two antibiotics may lead to the expression of virulence genes that are typically only transcribed in vivo, as well as only during late-log or stationary phase in vitro.