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Absence of SpeB production in virulent large capsular forms of group A streptococcal strain 64
R Raeder1, E Harokopakis, S Hollingshead
1Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43613-5806, USA.
Abstract:
Passage in human blood of group A streptococcal isolate 64p was previously shown to result in the enhanced expression of M and M-related proteins. Similarly, when this isolate was injected into mice via an air sac model for skin infection, organisms recovered from the spleens showed both increased expression of M and M-related proteins and increased skin-invasive potential. We show that these phenotypic changes were not solely the result of increased transcription of the mRNAs encoding the M and M-related gene products. Rather, the altered expression was associated with posttranslational modifications of the M and M-related proteins that occur in this strain, based on the presence or absence of another virulence protein, the streptococcal cysteine protease SpeB. The phenotypic variability also correlates with colony size variation. Large colonies selected by both regimens expressed more hyaluronic acid, which may explain differences in colony morphology. All large-colony variants were SpeB negative and expressed three distinct immunoglobulin G (IgG)-binding proteins in the M and M-related protein family. Small-colony variants were SpeB positive and bound little IgG through their M and M-related proteins because these proteins, although made, were degraded or altered in profile by the SpeB protease. We conclude that passage in either human blood or a mouse selects for a stable, phase-varied strain of group A streptococci which is altered in many virulence properties.
Insights
Passage in blood or mice alters group A streptococci virulence. This involves post-translational modification of M proteins, influenced by SpeB protease, affecting immunoglobulin G binding and invasion.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Group A Streptococcus (GAS) isolate 64p shows enhanced M and M-related protein expression after passage in human blood.
- In vivo passage in mice also increases M protein expression and skin invasiveness in GAS.
Purpose of the Study:
- To investigate the mechanisms behind enhanced M and M-related protein expression in GAS after host passage.
- To determine the role of post-translational modifications and the SpeB protease in GAS virulence factor expression and phenotypic variation.
Main Methods:
- Analysis of M and M-related protein expression and mRNA transcription.
- Investigation of post-translational modifications in the presence or absence of SpeB.
- Correlation of colony morphology and size with virulence factor expression and SpeB activity.
Main Results:
- Phenotypic changes are due to post-translational modifications, not solely increased mRNA transcription.
- The streptococcal cysteine protease SpeB influences M and M-related protein stability and immunoglobulin G (IgG) binding.
- Large-colony variants (SpeB-negative) express more hyaluronic acid and bind more IgG, while small-colony variants (SpeB-positive) show SpeB-mediated degradation of M proteins.
Conclusions:
- Host passage selects for stable, phase-varied GAS strains with altered virulence properties.
- SpeB protease activity is a key factor in GAS phenotypic variation and virulence modulation.
- Post-translational regulation of M proteins by SpeB impacts bacterial interaction with host immunity (IgG binding).