title: Genes for the majority of group a streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease.
abstract: BACKGROUND
  The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease.
  
  
  METHODS
  In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease.
  
  
  RESULTS
  Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study.
  
  
  CONCLUSIONS
  Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/or host factors.
authors.affiliation: German Research Centre for Biotechnology, Braunschweig, Germany. david.mcmillan@qimr.edu.au
authors.forename: David J
authors.initials: DJ
authors.lastname: McMillan
authors.forename: R G
authors.initials: RG
authors.lastname: Beiko
authors.forename: R
authors.initials: R
authors.lastname: Geffers
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: L M
authors.initials: LM
authors.lastname: Schouls
authors.forename: B J M
authors.initials: BJ
authors.lastname: Vlaminckx
authors.forename: W J B
authors.initials: WJ
authors.lastname: Wannet
authors.forename: K S
authors.initials: KS
authors.lastname: Sriprakash
authors.forename: G S
authors.initials: GS
authors.lastname: Chhatwal
mesh_terms: D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013290:Streptococcal Infections / Q000378:metabolism* / Q000503:physiopathology; D013291:Streptococcus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D037521:Virulence Factors