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Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.

ABSTRACT: Group A streptococci can be categorized into two classes (I and II) based on immunodeterminants contained within a surface-exposed, conserved region (C repeat domain) of the major virulence factor, M protein. Previous studies have shown that several biological properties correlate strongly with streptococcal class, and thus, there is a strong impetus to precisely define the antigenic epitopes unique to class I and II M proteins. Using synthetic peptides, the binding sites of two class I-specific mAbs were mapped to distinct epitopes within the C repeat region of type 6 M protein (class I). A class II M protein-like gene (type 2) was cloned and sequenced, and the predicted amino acid sequence was compared for homology to class I and II molecules, whose sequences were previously reported. For a given C repeat block 35 amino acid residues in length, 20 residue positions were conserved among all sequences analyzed. Of the 15 variable amino acid positions, only four were class specific, and three of the four positions were localized in the area to which the class I-specific mAbs bound. The predicted secondary structures of class I and II C repeat blocks reveals that they are alpha-helical, except for a single area of disruption. In the class I molecules, the area of disruption corresponds to the class I-specific mAb binding sites. Importantly, the predicted conformational characteristics of this disruption differs for class I and II molecules. The data suggest that only limited changes in amino acid residues differentiate between class I and II molecules in the C repeat region. Therefore, selective (biological) pressures may have contributed to the evolution of these two classes of molecules.

SUBMITTER: Bessen DE

PROVIDER: S-EPMC2188760 | biostudies-other | 1990 Dec

REPOSITORIES: biostudies-other

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Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.

Bessen D E DE Fischetti V A VA

The Journal of experimental medicine 19901201 6

Group A streptococci can be categorized into two classes (I and II) based on immunodeterminants contained within a surface-exposed, conserved region (C repeat domain) of the major virulence factor, M protein. Previous studies have shown that several biological properties correlate strongly with streptococcal class, and thus, there is a strong impetus to precisely define the antigenic epitopes unique to class I and II M proteins. Using synthetic peptides, the binding sites of two class I-specific ...[more]

PMID: 2258705

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Project description:Streptococcus dysgalactiae subsp. equeisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe and US. Although SDSE possesses similar virulence factors to S. pyogenes including streptolysin S (SLS) and streptolysin O (SLO), some important S. pyogenes virulence factors including active superantigens, SpeB and a hyarulonic acids capsule are missing in SDSE genome. The mechanisms and the key virulence factors for causing invasive diseases by SDSE are poorly understood. Here, we analyzed the transcriptome of SDSE in vivo using the murine sepsis model, revealing the strategy of SDSE to destruct host tissues with the virulence factors and to scavenge depleted nutrients. The expression of SLO operon increased at relatively early stage of infection while the SLS and hyaluronidases upregulated after 4h post infection. Microarray data suggested that SDSE degraded host tissue polysaccharides by streptococcal-secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expressions of genes encoding SLS and the carbohydrate metabolism enzymes. Moreover, csrS deficient mutant induced sever systemic hemolysis in mice. The most frequently isolated stG6792 strains from invasive disease secreted abundant SLS and SLO rather than other SDSE emm types, indicating the relationship between the SLS and SLO productions and poor outcome by the stG6792 strain infection. Our findings suggest that the concomitant regulation of virulence factors destructing the host tissues and metabolic enzymes play an important role to produce invasive diseases by SDSE. To analyze gene expressions in group G streptococci with the murine infection model, we developed a custom microarray for Streptococcus dysgalactiae subsp. equisimilis (SDSE) based on the genome sequences of three SDSE strains; GGS_124, ATCC12923 and RE378. We intraperitoneally inoculated 10^8 CFU of GGS_124 stain and the csrS deficient mutant into ddY mice. Bacterial cells were collected from the abdominal cavity at 0, 2, 4 and 8 h post infection. GGS_124 cells were also collected from OD600=0.6 culture in brain heart infusion broth as a control.

Dataset Information

Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.

Publications

Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.

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