U.S. Department of Energy

Pacific Northwest National Laboratory

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

TitleSystems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella.
Publication TypeJournal Article
Year of Publication2011
AuthorsYoon H, Ansong C, McDermott JE, Gritsenko M, Smith RD, Heffron F, Adkins JN
JournalBMC Syst Biol
KeywordsAlgorithms, Animals, Bacterial Proteins, Cytoplasm, Female, Gene Deletion, Gene Expression Profiling, Mice, Protein Transport, Proteomics, Reproducibility of Results, Salmonella, Sequence Homology, Amino Acid, Systems Biology, Virulence Factors
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.

DOI10.1186/1752-0509-5-100
Alternate JournalBMC Syst Biol
PubMed ID21711513
PubMed Central IDPMC3213010
Grant ListP41 RR018522 / RR / NCRR NIH HHS / United States
P41 RR018522-08 / RR / NCRR NIH HHS / United States
R01 AI022933 / AI / NIAID NIH HHS / United States
RR 018522 / RR / NCRR NIH HHS / United States
Y1-AI-4894-01 / AI / NIAID NIH HHS / United States
Y1-AI-8401-01 / AI / NIAID NIH HHS / United States
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