Affiliation:
1. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
2. Department of Pathological Anatomy, Faculty of Medicine, La Frontera University, Temuco, Chile
Abstract
ABSTRACT
In a previous study, a novel virulence gene,
bstA
, identified in a
Salmonella enterica
serovar Typhimurium sequence type 313 (ST313) strain was found to be conserved in all published
Salmonella enterica
serovar Dublin genomes. In order to analyze the role of this gene in the host-pathogen interaction in
S
. Dublin, a mutant where this gene was deleted (
S
. Dublin Δ
bstA
) and a mutant which was further genetically complemented with
bstA
(
S
. Dublin 3246-C) were constructed and tested in models of
in vitro
and
in vivo
infection as well as during growth competition assays in M9 medium, Luria-Bertani broth, and cattle blood. In contrast to the results obtained for a strain of
S
. Typhimurium ST313, the lack of
bstA
was found to be associated with increased virulence in
S
. Dublin. Thus,
S
. Dublin Δ
bstA
showed higher levels of uptake than the wild-type strain during infection of mouse and cattle macrophages and higher net replication within human THP-1 cells. Furthermore, during mouse infections,
S
. Dublin Δ
bstA
was more virulent than the wild type following a 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 the cytotoxicity toward these cells. The histology of the livers and spleens of mice infected with the wild-type strain and the
S
. Dublin Δ
bstA
mutant revealed similar levels of inflammation between the two groups. The gene was not important for adherence to or invasion of human epithelial cells and did not influence bacterial growth in rich medium, minimal medium, or cattle blood. In conclusion, a lack of
bstA
affects the pathogenicity of
S
. Dublin by decreasing its virulence. Therefore, it might be regarded as an antivirulence gene in this serovar.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
14 articles.
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