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Properties of IgG-binding proteins expressed by Streptococcus pyogenes isolates are predictive of invasive potential
Abstract:
Recent clinical Streptococcus pyogenes isolates of the M1 serotype can be grouped according to the IgG-binding properties of their M proteins. One group expressed an IgG-binding M1 protein reactive with human IgG1, IgG2, IgG3, and IgG4 (type IIo); the other expressed a protein with predominant reactivity with human IgG3 alone (type IIb). Both IgG-binding protein phenotypes were equally resistant to phagocytosis in human blood; however, when they were injected into a skin air sac on outbred CD1 mice, all mice injected with M1 isolates of the type IIo phenotype were dead within 70 h, while only 40% of those injected with M1 isolates of the type IIb phenotype died within the same period. Bacteria recovered from the spleens of animals that died after injection with type IIb phenotype isolates demonstrated a change in their IgG-binding profile and were indistinguishable, in vitro or in vivo, from isolates displaying the type IIo phenotype.
Insights
Streptococcus pyogenes M1 serotype strains show varied IgG-binding. Type IIo strains, binding multiple IgG types, caused higher mortality in mice than type IIb strains, which bind primarily IgG3.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Streptococcus pyogenes M1 serotype isolates exhibit distinct IgG-binding M protein phenotypes.
- These phenotypes, type IIo (broad IgG reactivity) and type IIb (IgG3 predominant reactivity), influence bacterial virulence.
Purpose of the Study:
- To investigate the in vivo virulence differences between Streptococcus pyogenes M1 serotype isolates with type IIo and type IIb IgG-binding M protein phenotypes.
Main Methods:
- Comparison of phagocytosis resistance in human blood for both phenotypes.
- Infection model using a skin air sac in CD1 mice to assess mortality rates.
- Analysis of IgG-binding profiles of bacteria recovered from infected mice.
Main Results:
- Both type IIo and type IIb M1 isolates were equally resistant to phagocytosis in human blood.
- Type IIo isolates demonstrated significantly higher mortality rates in mice compared to type IIb isolates within 70 hours.
- Recovered type IIb bacteria from infected mice showed altered IgG-binding profiles, resembling type IIo isolates.
Conclusions:
- The IgG-binding profile of Streptococcus pyogenes M1 serotype M proteins is a critical factor in determining in vivo virulence.
- The type IIb phenotype, despite initial lower virulence, can adapt and acquire the more virulent type IIo phenotype during infection.