Antigenic variation among group A streptococcal M proteins. Nucleotide sequence of the serotype 5 M protein gene and its relationship with genes encoding types 6 and 24 M proteins
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1Department of Microbiology, Medical School, University of Newcastle upon Tyne, United Kingdom.
Abstract:
The 1479-base pair (bp) nucleotide sequence of the serotype 5 M protein gene (smp5) from Streptococcus pyogenes contains three distinct types of tandemly repeated sequences, designated A, B, and C. Repeat A (21 bp x 6, in the 5'-half of smp5), shares no homology with the types 6 or 24 M protein genes (Hollingshead, S. K., Fischetti, V. A., and Scott, J. R. (1986) J. Biol. Chem. 261, 1677-1686; Mouw, A. R., Beachey, E. H., and Burdett, V. (1988) J. Bacteriol., in press). Repeat B (75 bp x 3.6, in the center of smp5) is also present in the M6, but not in the M24 gene. Repeat C (105 bp x 2.7, just distal to the B repeats) shares homology with repeats in both the M6 and M24 genes. All three genes share extensive homology in their 3'-halves and in 5' sequences encoding the N-terminal signal peptides, but between these two regions there are highly variable sequences that are responsible for antigenic diversity. These relationships suggest that both intergenic and intragenic recombination has occurred during the evolution of distinct M protein serotypes. All three M proteins contain conserved hydrophobic and proline-rich sequences at their C-terminal ends, suggestive of a membrane anchor and a peptidoglycan spanning region.
Insights
The Streptococcus pyogenes serotype 5 M protein gene (smp5) has unique tandem repeats. Sequence analysis suggests recombination events shaped M protein diversity, with conserved C-terminal regions indicating functional roles.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Streptococcus pyogenes M proteins are key virulence factors involved in host immune evasion.
- M protein diversity is linked to antigenic variation, allowing the pathogen to evade host immunity.
- Understanding M protein gene structure provides insights into bacterial evolution and pathogenesis.
Purpose of the Study:
- To analyze the nucleotide sequence of the serotype 5 M protein gene (smp5) from Streptococcus pyogenes.
- To identify and characterize repeated sequences within the smp5 gene.
- To investigate the evolutionary relationships between different M protein serotypes based on sequence homology.
Main Methods:
- Nucleotide sequencing of the 1479-base pair (bp) smp5 gene.
- Comparative sequence analysis of smp5 with M protein genes from serotypes 6 and 24.
- Identification and characterization of tandemly repeated sequences (A, B, and C) within smp5.
Main Results:
- The smp5 gene contains three distinct types of tandemly repeated sequences: A, B, and C.
- Repeat A shows no homology with M6 or M24 genes, while Repeat B is found in M6 but not M24.
- Repeat C shares homology with repeats in both M6 and M24 genes, indicating shared evolutionary origins.
- Extensive homology exists in the 5' (signal peptide) and 3' gene halves, with variable central regions contributing to antigenic diversity.
- Conserved hydrophobic and proline-rich C-terminal sequences suggest a role in membrane anchoring and peptidoglycan binding.
Conclusions:
- The structural organization of the smp5 gene, particularly its repeat regions, provides evidence for intergenic and intragenic recombination in M protein evolution.
- Sequence variations in the central regions of M protein genes are critical for generating antigenic diversity among Streptococcus pyogenes serotypes.
- Conserved C-terminal domains likely play essential roles in M protein function, such as cell wall anchoring and interaction with host tissues.