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

Hyunjin Yoon, Charles Ansong, Jason E. McDermott, Marina Gritsenko, Richard D. Smith, Fred Heffron, Joshua N. Adkins

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    22 Scopus citations

    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.

    Original languageEnglish (US)
    Article number100
    JournalBMC Systems Biology
    Volume5
    DOIs
    Publication statusPublished - Jun 28 2011

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    ASJC Scopus subject areas

    • Molecular Biology
    • Structural Biology
    • Applied Mathematics
    • Modeling and Simulation
    • Computer Science Applications

    Cite this

    Yoon, H., Ansong, C., McDermott, J. E., Gritsenko, M., Smith, R. D., Heffron, F., & Adkins, J. N. (2011). Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella. BMC Systems Biology, 5, [100]. https://doi.org/10.1186/1752-0509-5-100