Review of the Food-borne Zoonoses Research ... - ARCHIVE: Defra

Project code: OZ0315
Project title: Salmonella pathogenesis and immunity in cattle and
pigs
Start date (dd/mm/yy): 01/04/1999
End date (dd/mm/yy): 30/06/2002
£656,100
Total cost:
Affiliation: Institute for Animal Health, Compton
Abstract of research
Salmonella enterica subspecies I is an important cause of enteric disease in man and
farmed livestock. Infections often involve acute enteritis and may be complicated by lifethreatening
systemic sequelae depending on serovar- and host-specific factors. In the
absence of effective vaccines, control and therapy of Salmonellosis in livestock relies on
fluid replacement and antibiotic use. Widespread concern exists that the latter may lead
to an increase in transmissible antibiotic resistance. Toward the development of
intervention strategies not reliant on antibiotic use, Defra project OZ0315 aimed to
identify and characterize factors influencing Salmonella pathogenesis and host
responses in cattle and pigs. We characterized a panel of S. enterica serovars of
differing virulence in calves and pigs and observed that systemic virulence correlated
with enhanced persistence in mesenteric lymph nodes but not the response of primary
macrophages infected ex vivo. The cell tropism of S. enterica serovars in the bovine
intestinal mucosa was also examined and host cell-killing by a novel caspase-dependent
mechanism distinct from apoptosis characterized. Systemic translocation of S. Dublin in
calves was observed to occur via efferent lymphatics, but not venous blood, in a cell-free
niche. By targeted and genome-wide mutagenesis factors influencing both the enteric
and systemic virulence of Salmonella in calves and pigs were identified, providing
valuable data for the rational attenuation of Salmonella for use as live vaccines.
Review Summary
This was a good, practical project with an excellent output of 18 published papers. It had
provided information on the molecular basis of salmonella pathogenesis in cattle and
pigs and had the potential to assist with control by providing data for the rational
development of live vaccines. However, it was noted that while this was high-quality
science, it was, for Defra‘s purposes, quite distant from practical applications.
The contractors had much expertise in the area and used novel techniques to further
develop the work. There was progress towards identifying suitable vaccine candidates,
but the project leader has now left. Project OZ0319 was set up to address some of the
questions raised by this study.
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