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Title:   Author  item
                                            Brunelle, Brianitem
                                            Bearson, Shawnitem
                                            Bearson, Bradley

                                                         - *Brad*
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 7/12/2013
                                    Publication  Date: 7/22/2013
                                    Citation: Brunelle, B.W., Bearson, S.M., Bearson, B.L. 2013. Transcriptomic analysis of multidrug-resistant Salmonella enterica serovar Typhimurium isolates that exhibit a tetracycline-induced invasion phenotype [abstract]. Molecular Genetics of Bacteria and Phage Meeting. p. 221.Interpretive Summary:
                                Technical Abstract: Salmonella is a highly prevalent bacterial food-borne disease in the U.S. and is estimated to cause over 1 million cases, 19,000 hospitalizations, and 350 deaths every year.  Multidrug-resistant (MDR) Salmonella has emerged as an important food safety concern as it is associated with increased morbidity in humans relative to sensitive strains. Salmonella enterica serovar Typhimurium is one of the most common salmonellae in humans and livestock, and many of these cases are found to be resistant to several antibiotics; resistance to tetracycline in particular is prominent among S. Typhimurium isolates from humans (34 per cent), chickens (39 per cent), cattle (59 per cent), and swine (88 per cent) according to a ten-year average from the National Antimicrobial Resistance Monitoring System (NARMS). Our goal was to identify and characterize the effect of tetracycline on the invasiveness of MDR S. Typhimurium. Under typical in vitro growth conditions, genes associated with motility are expressed during early-log growth, while genes correlated with invasion, attachment, and intracellular survival are expressed during late-log or stationary growth phase. Using tissue culture assays, a subset of MDR S. Typhimurium isolates were identified that induced invasion during the early-log growth phase after exposure to sub-inhibitory levels of tetracycline.  Global gene expression changes due to tetracycline in early-invasive MDR S. Typhimurium were assessed by RNA-seq. The transcriptomic data revealed that genes associated with motility were down-regulated, but genes involved in attachment, invasion, and intracellular survival were up-regulated due to tetracycline exposure. Thus, pathways that are characteristically up-regulated in late-log growth phase were stimulated by tetracycline to occur during early-log growth.  Our data indicate that exposure to sub-inhibitory concentrations of tetracycline induces the invasiveness of certain Salmonella isolates by accelerating the temporally regulated pathways that enable cellular entry, which may confer a selective advantage in the host. Because tetracycline is often administered to humans and livestock, characterizing its effects on Salmonella invasiveness and virulence will enhance our understanding of its impact on both animal and human health.


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