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Streptococcus pneumoniae type 3 encodes a protein highly similar to the human glutamate decarboxylase (GAD65)
1Departamento de Microbiología Molecular, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Abstract:
A 2.5-kb ScaI fragment of the type 3 pneumococcal strain 406 DNA containing a 1425-nucleotide open reading frame (gadA) and encoding a 475-amino acid protein (M(r) 54,427) was characterised. The gene gadA was expressed in Salmonella typhimurium. Pulsed-field gel electrophoresis and Southern blotting analysis of DNAs prepared from several pneumococcal serotypes showed that only those clinical isolates belonging to serotype 3 harbour the gadA gene. Sequence comparison of GadA with proteins included in the data banks revealed the highest similarity with human glutamate decarboxylase (GAD65) (59% similarity, 28% identity). Auto-antibodies to GAD65 have been associated with the onset of insulin-dependent diabetes mellitus. Interestingly, several epitopes of GAD65 that have been identified as immunodominant are particularly well conserved in the pneumococcal GadA.
Insights
Pneumococcal type 3 strains possess a gadA gene encoding a protein similar to human glutamate decarboxylase (GAD65). This finding may have implications for understanding autoimmune responses, as GAD65 is linked to diabetes.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- The Streptococcus pneumoniae gadA gene encodes a protein with structural similarities to human GAD65.
- Autoantibodies against human GAD65 are implicated in the development of insulin-dependent diabetes mellitus.
Purpose of the Study:
- To characterize the pneumococcal gadA gene and its protein product.
- To investigate the prevalence of the gadA gene in different pneumococcal serotypes.
- To explore potential immunological connections between pneumococcal GadA and human GAD65.
Main Methods:
- DNA characterization using ScaI restriction fragments.
- Gene expression in Salmonella typhimurium.
- Pulsed-field gel electrophoresis and Southern blotting for gene detection.
- Sequence comparison with existing protein databases.
Main Results:
- A 2.5-kb DNA fragment containing the 1425-nucleotide gadA gene was identified and characterized.
- The gadA gene was successfully expressed in Salmonella typhimurium.
- The gadA gene was found exclusively in Streptococcus pneumoniae serotype 3 clinical isolates.
- Pneumococcal GadA showed significant sequence similarity to human GAD65, particularly in immunodominant epitope regions.
Conclusions:
- The gadA gene is specific to Streptococcus pneumoniae serotype 3.
- The pneumococcal GadA protein shares conserved epitopes with human GAD65, suggesting potential cross-reactivity.
- This research opens avenues for investigating the role of pneumococcal GadA in autoimmune diseases.