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

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Project code: OZ0319<br />

Project title: Salmonella pathogenesis in cattle and pigs<br />

Start date (dd/mm/yy): 01/07/2002<br />

End date (dd/mm/yy): 30/09/2006<br />

£709,200<br />

Total cost:<br />

Affiliation: Institute for Animal Health, Compton<br />

Sub-contractor(s): None<br />

Abstract <strong>of</strong> research<br />

Salmonella enterica is an enteric bacterial pathogen <strong>of</strong> worldwide importance. Over<br />

2500 distinct serovars <strong>of</strong> S. enterica exist and <strong>the</strong>se can be divided into three broad<br />

types; ubiquitous serovars that can cause acute but self-limiting gastroenteritis in a broad<br />

range <strong>of</strong> hosts (e.g. S. Typhimurium), host-restricted serovars that exhibit a preference<br />

for a narrower range <strong>of</strong> hosts (e.g. S. Dublin and S. Choleraesuis) and host-specific<br />

serovars that produce disease in only one host (e.g. S. Typhi in humans). Host-restricted<br />

and -specific serovars <strong>of</strong>ten cause only mild enteritis but possess <strong>the</strong> ability to<br />

disseminate from <strong>the</strong> intestines to <strong>the</strong> organs <strong>of</strong> <strong>the</strong> body, causing typhoid fever-like<br />

illnesses in animals that may be severe and life-threatening. Non-typhoidal Salmonellosis<br />

caused by ubiquitous serovars also poses serious welfare and economic problems for<br />

livestock producers. Moreover, Salmonella infection <strong>of</strong> pigs and cattle can lead to entry <strong>of</strong><br />

<strong>the</strong> pathogen into <strong>the</strong> food chain and environment, providing an important reservoir <strong>of</strong><br />

human infection. The molecular mechanisms underlying <strong>the</strong> ability <strong>of</strong> Salmonella enterica<br />

to colonise <strong>the</strong> intestines <strong>of</strong> food-producing animals, induce enteritis and in some cases<br />

translocate to distal sites, are poorly understood. <strong>Defra</strong>-funded research conducted<br />

under project OZ0319 aimed to understand <strong>the</strong>se processes in greater detail and to use<br />

<strong>the</strong> knowledge to develop, test and refine novel methods <strong>of</strong> disease control. Such<br />

research led to <strong>the</strong> testing <strong>of</strong> subunit vaccines in pigs, live-attenuated vaccines in calves<br />

and analysis <strong>of</strong> <strong>the</strong> protective efficacy <strong>of</strong> small molecule inhibitors that disarm a key<br />

Salmonella virulence factor.<br />

<strong>Review</strong> Summary<br />

Innovative and novel methodologies were used to examine <strong>the</strong> pathogenesis <strong>of</strong><br />

salmonella in cattle and pigs, including factors that play conserved roles in colonisation <strong>of</strong><br />

calves, pigs and chickens, and host-specific colonisation factors. The researchers<br />

identified cytokine responses <strong>of</strong> <strong>the</strong> intestinal mucosa following infection with S.<br />

Typhimurium and <strong>the</strong> host-specific serovars, S. Dublin and S. Choleraesuis. The project<br />

included an examination <strong>of</strong> <strong>the</strong> basis <strong>of</strong> attenuation <strong>of</strong> mutant strains in vitro and in<br />

animals. The researchers fur<strong>the</strong>r examined <strong>the</strong> efficacy <strong>of</strong> a subunit vaccine that<br />

comprised S. Typhimurium Type III secreted proteins in pigs, and <strong>the</strong> ability <strong>of</strong> smallmolecule<br />

inhibitors <strong>of</strong> Type III secretion to block Salmonella-induced Enteritis.<br />

Although <strong>the</strong> study has increased background knowledge, for this project to be really<br />

relevant to <strong>Defra</strong>, it also needed to attract <strong>the</strong> interest and funding <strong>of</strong> <strong>the</strong> wider<br />

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