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Identification and characterization of an antigen I/II family protein produced by group A Streptococcus

Shizhen Zhang1, Nicole M Green, Izabela Sitkiewicz

  • 1Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, The Methodist Hospital, B154, 6565 Fannin St., Houston, TX 77030, USA.

Infection and Immunity
|June 23, 2006
PubMed

Insights

Group A Streptococcus (GAS) invasive infections are linked to a novel genetic element, RD2. A key protein, Spy1325, found on the bacterial surface, shows potential as a shared virulence factor and vaccine target against GAS and related bacteria.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Genomics

Background:

  • Group A Streptococcus (GAS) causes diverse human infections, with M28 serotype strains frequently linked to severe invasive disease, including puerperal sepsis.
  • Genomic analysis of M28 GAS revealed a novel foreign genetic element, region of difference 2 (RD2), similar to genomic islands in Group B Streptococcus (GBS).
  • RD2 encodes seven proteins, including Spy1325, a newly characterized antigen I/II family protein with potential implications for inter-species virulence.

Purpose of the Study:

  • To characterize the novel RD2 element and its encoded proteins in Group A Streptococcus.
  • To investigate the expression, localization, and potential role of the Spy1325 protein in GAS pathogenesis.
  • To evaluate Spy1325 as a potential vaccine candidate against GAS infections.

Main Methods:

  • Genome sequencing of M28 GAS strain and identification of the RD2 element.
  • PCR and DNA sequencing to assess Spy1325 gene conservation across GAS serotypes.
  • Real-time quantitative PCR, Western immunoblotting, and ELISA to determine Spy1325 gene expression and protein presence in vitro and in vivo.
  • Immunization of mice with recombinant Spy1325 fragments and assessment of protection against GAS challenge.
  • Biochemical assays to analyze Spy1325 binding to human salivary agglutinin.

Main Results:

  • The novel 37.4-kb RD2 element was identified in M28 GAS strains.
  • The Spy1325 gene is highly conserved across different GAS serotypes and is expressed by GAS in vitro and in vivo.
  • Spy1325 protein is present in culture supernatants and on the GAS cell surface, and is detected in infected hosts.
  • Immunization with Spy1325 conferred protection against GAS-induced mortality in mice.
  • Spy1325 demonstrated binding to human salivary agglutinin, similar to other antigen I/II proteins.

Conclusions:

  • Spy1325, encoded by the novel RD2 element, is a conserved, surface-exposed protein in GAS.
  • Spy1325 is a potential shared virulence factor among GAS, GBS, and oral streptococci.
  • Spy1325 represents a promising vaccine candidate for preventing invasive Group A Streptococcus infections.

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