title: Determination of the relationship between group A streptococcal genome content, M type, and toxic shock syndrome by a mixed genome microarray.
abstract: Group A streptococci (GAS), or Streptococcus pyogenes, are associated with a remarkable variety of diseases, ranging from superficial infections to life-threatening diseases such as toxic-shock-like syndrome (TSS). GAS strains belonging to M types M1 and M3 are associated with TSS. This study aims to obtain insight into the gene profiles underlying different M types and disease manifestations. Genomic differences between 76 clinically well characterized GAS strains collected in The Netherlands were examined using a mixed-genome microarray. Inter-M-type genomic differences clearly outweighed intra-M-type genome variation. Phages were major contributors to observed genome diversification. We identified four novel genes, including two genes encoding fibronectin-binding-like proteins, which are highly specific to a subset of M types and thus may contribute to M-type-associated disease manifestations. All M12 strains were characterized by the unique absence of the citrate lyase complex and reduced growth under hypoxic, nutrient-deprived conditions. Furthermore, six virulence factors, including genes encoding a complement-inhibiting protein (sic), an exotoxin (speA), iron(III) binding factor, collagen binding factor (cpa), and fibrinogen binding factor (prt2-like), were unique to M1 and/or M3 strains. These virulence factors may contribute to the potential of these strains to cause TSS. Finally, in contrast to M-type-specific virulence profiles, we did not identify a common virulence profile among strains associated with TSS irrespective of their M type.
authors.affiliation: University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. B.J.M.Vlaminckx@lab.azu.nl
authors.forename: Bart J M
authors.initials: BJ
authors.lastname: Vlaminckx
authors.forename: Frank H J
authors.initials: FH
authors.lastname: Schuren
authors.forename: Roy C
authors.initials: RC
authors.lastname: Montijn
authors.forename: Martien P M
authors.initials: MP
authors.lastname: Caspers
authors.forename: Ad C
authors.initials: AC
authors.lastname: Fluit
authors.forename: Wim J B
authors.initials: WJ
authors.lastname: Wannet
authors.forename: Leo M
authors.initials: LM
authors.lastname: Schouls
authors.forename: Jan
authors.initials: J
authors.lastname: Verhoef
authors.forename: Wouter T M
authors.initials: WT
authors.lastname: Jansen
mesh_terms: D000942:Antigens, Bacterial / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012772:Shock, Septic / Q000382:microbiology / Q000503:physiopathology*; D013290:Streptococcal Infections / Q000382:microbiology / Q000503:physiopathology; D013297:Streptococcus pyogenes / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D037521:Virulence Factors; C014689:streptococcal M protein