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Open Access Highly Accessed Research article

Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

Hyunjin Yoon1, Charles Ansong2, Jason E McDermott2, Marina Gritsenko2, Richard D Smith2, Fred Heffron1 and Joshua N Adkins2*

Author affiliations

1 Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239, USA

2 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA

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Citation and License

BMC Systems Biology 2011, 5:100  doi:10.1186/1752-0509-5-100

Published: 28 June 2011

Abstract

Background

Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity.

Results

In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism.

Conclusions

Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.