title: Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Yoon
authors.forename: Charles
authors.initials: C
authors.lastname: Ansong
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Marina
authors.initials: M
authors.lastname: Gritsenko
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Fred
authors.initials: F
authors.lastname: Heffron
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
mesh_terms: D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D051379:Mice; D021381:Protein Transport; D040901:Proteomics; D015203:Reproducibility of Results; D012475:Salmonella / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D049490:Systems Biology / Q000379:methods*; D037521:Virulence Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors