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Determination of the relationship between group A streptococcal genome content, M type, and toxic shock syndrome by a mixed genome microarray

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Author: Vlaminckx, B.J.M. · Schuren, F.H.J. · Montijn, R.C. · Caspers, M.P.M. · Fluit, A.C. · Wannet, W.J.B. · Schouls, L.M. · Verhoef, J. · Jansen, W.T.M.
Institution: TNO Kwaliteit van Leven
Source:Infection and Immunity, 5, 75, 2603-2611
Identifier: 239950
doi: doi:10.1128/IAI.01291-06
Keywords: Biology · Biotechnology · citric acid · collagen binding factor · complement inhibiting protein · exotoxin · ferric ion · fibrinogen binding factor · iron binding protein · lyase · speA protein · virulence factor · article · bacterial strain · bacterial virulence · bacteriophage · controlled study · DNA fingerprinting · DNA microarray · gene identification · genetic association · genetic code · genetic variability · genome · genomics · human · hypoxia · major clinical study · microbial diversity · Netherlands · nucleotide sequence · priority journal · Streptococcus group A · toxic shock syndrome · Antigens, Bacterial · Bacterial Outer Membrane Proteins · Bacterial Proteins · Carrier Proteins · Electrophoresis, Gel, Pulsed-Field · Gene Expression Profiling · Genome, Bacterial · Humans · Image Processing, Computer-Assisted · Oligonucleotide Array Sequence Analysis · Shock, Septic · Streptococcal Infections · Streptococcus pyogenes · Virulence Factors


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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.