3 years ago

The homolog of the gene bstA of the BTP1 phage from Salmonella Typhimurium ST313 is an antivirulence gene in S. Dublin.

Ana Herrero-Fresno, Priscila Regina Guerra, Malene Roed Spiegelhauer, Karsten Wiber Andersen, Irene Cartas Espinel, John Elmerdahl Olsen
In a previous study, a novel virulence gene, bstA, identified in S Typhimurium ST313, was found to be conserved in all published S Dublin genomes. In order to analyze the role of this gene in host-pathogen interaction in S. Dublin, mutants where this gene was deleted (SDΔbstA) and further genetically complemented (SD3246-C) were constructed and tested in in vitro and in vivo infection models as well as during growth competition assays in M9, LB and cattle blood. In contrast to the results obtained for a strain of S Typhimrium ST313, the lack of bstA was found to be associated with increased virulence in S. Dublin. Thus, SDΔbstA showed higher uptake levels than the wild-type during infection of mouse and cattle macrophages, and higher net replication within THP-1 human cells. Furthermore, during mice infections, SDΔbstA was more virulent than the wild-type following single intraperitoneal infection and showed an increased competitive index during competitive infection assays. Deletion of bstA did not affect either the amount of cytokines released by THP-1 macrophages or cytotoxicity towards these cells. Histology of the liver and spleen of wild-type and SDΔbstA infected mice revealed similar levels of inflammation between the two groups. The gene was not important for adhesion and invasion of human epithelial cells and did not influence bacterial growth in rich medium, minimal medium or cattle blood. In conclusion, lack of bstA affects pathogenicity of S. Dublin by decreasing virulence. Therefore, it might be regarded as an antivirulence gene in this serovar.

Publisher URL: http://doi.org/10.1128/IAI.00784-17

DOI: 10.1128/IAI.00784-17

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