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The streptococcal superantigen SMEZ exhibits wide allelic variation, mosaic structure, and significant antigenic
T Proft1, S L Moffatt, K D Weller
1Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand.
Abstract:
The frequencies of the newly identified streptococcal superantigen genes smez, spe-g, and spe-h were determined in a panel of 103 clinical isolates collected between 1976 and 1998 at various locations throughout New Zealand. smez and spe-g were found in every group A Streptococcus (GAS) isolate, suggesting a chromosomal location. The spe-h gene was found in only 24% of the GAS isolates and is probably located on a mobile DNA element. The smez gene displays extensive allelic variation and appears to be in linkage equilibrium with the M/emm type. 22 novel smez alleles were identified from 21 different M/emm types in addition to the already reported alleles smez and smez-2 with sequence identities between 94. 5 and 99.9%. Three alleles are nonfunctional due to a single base pair deletion. The remaining 21 alleles encode distinct SMEZ variants. The mosaic structure of the smez gene suggests that this polymorphism has arisen from homologous recombination events rather than random point mutation. The recently resolved SMEZ-2 crystal structure shows that the polymorphic residues are mainly surface exposed and scattered over the entire protein. The allelic variation did not affect either Vbeta specificity or potency, but did result in significant antigenic differences. Neutralizing antibody responses of individual human sera against different SMEZ variants varied significantly. 98% of sera completely neutralized SMEZ-1, but only 85% neutralized SMEZ-2, a very potent variant that has not yet been found in any New Zealand isolate. SMEZ-specific Vbeta8 activity was found in culture supernatants of 66% of the GAS isolates, indicating a potential base for the development of a SMEZ targeting vaccine.
Insights
The study identified streptococcal superantigen genes in Group A Streptococcus (GAS) isolates from New Zealand. The smez gene showed significant variation, with potential for developing a SMEZ-targeting vaccine.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Streptococcal superantigens (SMEs) are virulence factors produced by Group A Streptococcus (GAS).
- Understanding the genetic diversity and distribution of these superantigens is crucial for disease pathogenesis and vaccine development.
Purpose of the Study:
- To determine the frequencies of newly identified streptococcal superantigen genes (smez, spe-g, spe-h) in clinical GAS isolates from New Zealand.
- To investigate the allelic variation of the smez gene and its potential impact on protein function and antigenicity.
Main Methods:
- Analysis of 103 clinical GAS isolates collected between 1976 and 1998.
- Molecular characterization of smez, spe-g, and spe-h genes, including sequencing and identification of novel alleles.
- Assessment of Vbeta specificity, potency, and antigenic differences of SMEZ variants.
- Evaluation of human serum antibody responses against different SMEZ variants.
Main Results:
- smez and spe-g genes were present in all GAS isolates, suggesting chromosomal location.
- spe-h gene was found in 24% of isolates, likely on a mobile element.
- 22 novel smez alleles were identified, exhibiting extensive allelic variation and mosaic structure.
- Allelic variation resulted in significant antigenic differences, affecting antibody neutralization, but not Vbeta specificity or potency.
- SMEZ-specific Vbeta8 activity was detected in 66% of isolates.
Conclusions:
- The smez gene is highly polymorphic in New Zealand GAS isolates, likely due to homologous recombination.
- Significant antigenic differences among SMEZ variants necessitate consideration for vaccine design.
- The prevalence of SMEZ-specific Vbeta8 activity suggests potential for developing a SMEZ-targeting vaccine.