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Role of sensory systems in Salmonella pathogenesis

Reference	BBS/E/I/00001431
Principal Investigator / Supervisor	Professor Mark Stevens
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	265,014
Status	Completed
Type	Institute Project
Start date	01/07/2009
End date	08/01/2011
Duration	18 months

Abstract

Salmonella enterica is an animal and zoonotic pathogen of worldwide importance. Infections may present in a variety of ways, from asymptomatic colonisation to inflammatory diarrhoea or typhoid depending on serovar- and host-specific factors. The molecular mechanisms underlying the ability of host-restricted and -specific serovars to translocate from the intestines to distal organs are ill-defined. By using bovine oral challenge and surgical models, we have shown that S. Dublin transits through varied cellular and anatomical niches in its natural host. Following invasion of enterocytes it is found within MHC class II+ cells in the lamina propria before arriving at draining lymph nodes by an ill-defined process. It exits these via efferent lymph vessels in a predominantly cell-free niche, but is later found inside cells in the liver and other organs. We have surveyed the role of tens of virulence-associated and S. Dublin-specific loci in systemic translocation by following the fate of defined signature-tagged mutants during these processes (Pullinger et al. 2007, 2008). However, it remains unclear how Salmonella adapts to the changing niches that it encounters. Gram-negative pathogens deploy a plethora of two-component sensory systems to modulate gene expression in response to extrinsic signals. Here, we seek to define the temporal and spatial role of such systems in S. Dublin pathogenesis in cattle. We will create a library of defined signature-tagged S. Dublin mutants lacking each sensor kinase and screen it during enteric and systemic phases of infection of the natural host. This will rely on use of bovine challenge and lymphatic cannulation models to capture bacteria as infection spreads in real-time. Non-polar sensor and regulator deletion mutants will be created to validate phenotypes and evaluate cross-talk between systems. Where time permits the genes sensitive to virulence-associated two-component systems will be defined and their induction in vivo confirmed.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbial Food Safety, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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