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Comparative virulence of Streptococcus pneumoniae strains with insertion-duplication, point, and deletion mutations
A M Berry1, A D Ogunniyi, D C Miller
1Molecular Microbiology Unit, Women's and Children's Hospital, North Adelaide, S.A., 5006, Australia.
Abstract:
Pneumolysin is a 471-amino-acid toxin produced by Streptococcus pneumoniae which has both cytolytic and complement activation properties. We have constructed a derivative of the type 2 S. pneumoniae strain D39 in which the portion of the pneumolysin gene encoding amino acids 55 to 437 has been deleted in-frame. The virulence of this strain (DeltaPly) was compared with those of wild-type D39, a pneumolysin insertion-duplication mutant (PLN-A), and a derivative (PdT) carrying a toxin gene with three point mutations known to abolish both cytolytic activity and complement activation. PdT was intermediate in virulence between D39 and either PLN-A or DeltaPly in a mouse intraperitoneal challenge model. This provides unequivocal evidence that pneumolysin has an additional property that is not abolished by point mutations which reduce cytotoxicity and complement activation to virtually undetectable levels.
Insights
Streptococcus pneumoniae pneumolysin is a toxin with cytolytic and complement activation properties. A modified strain lacking a key portion of the pneumolysin gene showed reduced virulence, indicating pneumolysin has additional virulence factors.
Area of Science:
- Microbiology
- Immunology
- Toxicology
Background:
- Pneumolysin is a major virulence factor of Streptococcus pneumoniae.
- It possesses cytolytic and complement activation properties.
- The full extent of pneumolysin's role in virulence is not completely understood.
Purpose of the Study:
- To investigate the role of pneumolysin in Streptococcus pneumoniae virulence.
- To determine if pneumolysin possesses additional virulence-associated properties beyond cytotoxicity and complement activation.
Main Methods:
- Construction of a Streptococcus pneumoniae D39 derivative strain (DeltaPly) with an in-frame deletion in the pneumolysin gene (amino acids 55-437).
- Comparison of the virulence of DeltaPly with wild-type D39, a pneumolysin insertion-duplication mutant (PLN-A), and a mutant with point mutations abolishing cytolytic activity (PdT).
- Assessment of virulence using a mouse intraperitoneal challenge model.
Main Results:
- The DeltaPly strain exhibited significantly reduced virulence compared to wild-type D39.
- The PdT strain, with point mutations, showed intermediate virulence between wild-type and the deletion mutant.
- These findings suggest pneumolysin has virulence-associated functions independent of its cytolytic and complement-activating activities.
Conclusions:
- Pneumolysin contributes to Streptococcus pneumoniae virulence through mechanisms beyond its known cytolytic and complement-activating functions.
- Targeting these additional properties could offer novel therapeutic strategies against pneumococcal infections.