Abstract
Salmonella enterica serovar Heidelberg (S. Heidelberg) can cause foodborne illness in humans following the consumption of contaminated meat and poultry products. Recent studies from our laboratory have demonstrated that certain S. Heidelberg isolated from food-animal sources harbor multiple transmissible plasmids with genes that encode antimicrobial resistance, virulence and a VirB4/D4 type-IV secretion system. This study examines the potential role of these transmissible plasmids in bacterial uptake and survival in intestinal epithelial cells and macrophages, and the molecular basis of host immune system modulation that may be associated with disease progression. A series of transconjugant and transformant strains were developed with different combinations of the plasmids to determine the roles of the individual and combinations of plasmids on virulence. Overall the Salmonella strains containing the VirB/D4 T4SS plasmids entered and survived in epithelial cells and macrophages to a greater degree than those without the plasmid, even though they carried other plasmid types. During entry in macrophages, the VirB/D4 T4SS encoding genes are up-regulated in a time-dependent fashion. When the potential mechanisms for increased virulence were examined using an antibacterial Response PCR Array, the strain containing the T4SS down regulated several host innate immune response genes which likely contributed to the increased uptake and survival within macrophages and epithelial cells.
Highlights
Pathogenic bacteria account for an estimated 3.6 million foodborne illnesses each year in the United States, with nearly a third (1.04 million) due to nontyphoidal Salmonella enterica [1]
Salmonella infections alone contribute around 35% of hospitalizations and 64% of deaths associated with bacterial foodborne pathogens [1]
The present study examined the role of plasmids in the bacterial uptake and survival of S
Summary
Pathogenic bacteria account for an estimated 3.6 million foodborne illnesses each year in the United States, with nearly a third (1.04 million) due to nontyphoidal Salmonella enterica [1]. Salmonella infections alone contribute around 35% of hospitalizations and 64% of deaths associated with bacterial foodborne pathogens [1]. Heidelberg outbreak that was traced back to contaminated ground turkey caused at least 130 infections in 34 states [4]. The strain associated with this outbreak was resistant to multiple antimicrobial agents, including ampicillin, tetracycline and in some cases streptomycin and gentamicin [4]. Heidelberg, including resistance to clinically important third generation cephalosporins, in foods, food production and processing environments, and isolates from human infections [6,7,8,9], which could limit the treatment options for patients with severe infections. S. Heidelberg is among the most detected serovars isolated from turkey-, chicken- and swine-related sources according to data from USDA’s National Veterinary Services
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