Salmonella enterica is one of the most common bacterial foodborne pathogens in the United States, causing illnesses that range from self-limiting gastroenteritis to more severe, life threatening invasive disease. Many Salmonella strains contain plasmids that carry virulence, antimicrobial resistance, and/or transfer genes which allow them to adapt to diverse environments, and these can include incompatibility group (Inc) FIB plasmids. This study was undertaken to evaluate the genomic and phenotypic characteristics of IncFIB-positive Salmonella enterica serovar Typhimurium isolates from food animal sources, to identify their plasmid content, assess antimicrobial resistance and virulence properties, and compare their genotypic isolates with more recently isolated S. Typhimurium isolates from food animal sources. Methods: We identified 71 S. Typhimurium isolates that carried IncFIB plasmids. These isolates were subjected to whole genome sequencing and evaluated for bacteriocin production, antimicrobial susceptibility, the ability to transfer resistance plasmids, and a subset was evaluated for their ability to invade and persist in intestinal human epithelial cells. Results: Approximately 30% of isolates (n = 21) displayed bacteriocin inhibition of Escherichia coli strain J53. Bioinformatic analyses using PlasmidFinder software confirmed that all isolates contained IncFIB plasmids along with multiple other plasmid replicon types. Comparative analyses showed that all strains carried multiple antimicrobial resistance genes and virulence factors including iron acquisition genes, such as iucABCD (75%), iutA (94%), sitABCD (76%) and sitAB (100%). In 17 cases (71%), IncFIB plasmids, along with other plasmid replicon types, were able to conjugally transfer antimicrobial resistance and virulence genes to the susceptible recipient strain. For ten strains, persistence cell counts (27%) were noted to be significantly higher than invasion bacterial cell counts. When the genome sequences of the study isolates collected from 1998–2003 were compared to those published from subsequent years (2005–2018), overlapping genotypes were found, indicating the perseverance of IncFIB positive strains in food animal populations. This study confirms that IncFIB plasmids can play a potential role in disseminating antimicrobial resistance and virulence genes amongst bacteria from several food animal species.
One of the key components to vertebrate survival is the innate ability to produce interferons (IFN). Type 1 IFN are regulatory proteins expressed in response to infection caused by invading viruses. The synthesis of these cytokines is upregulated through several different cellular pathways. For instance, the RIG‐I pathway detects foreign viral RNA enabling the CARD domains of RIG‐I to be ubiquitinized by the enzyme, TRIM25. This initiates a signaling cascade which ultimately results in the expression of IFN. Once produced, IFN are released from the infected cell and bind to IFN‐alpha/beta receptors on the epithelial cells of the respiratory system. This consequently produces antiviral cytokines which degrade viral RNA. In defense to this mechanism, Influenza A virus carries an NS1 gene that has been shown to compromise the regulation of IFN. NS1 binds to TRIM25, preventing the enzyme from ubiquitinating RIG‐I and ultimately inhibiting cytokine production. NS1, although not necessary for construction of the virus itself, compromises the innate immune system, resulting in the flu. The E.E. Waddell SMART Team (Students Modeling A Research Topic), in collaboration with MSOE, has built accurate models of IFN and NS1 using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.
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