Identification of novel pneumolysin alleles from paediatric carriage isolates of Streptococcus pneumoniae
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Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
Published on: September 11, 2020
J M C Jefferies1,2, A S Tocheva2, H Rubery3
1Health Protection Agency South East Regional Microbiology Laboratory, Southampton University Hospitals NHS Trust, Southampton SO16 6YD, UK.
Insights
Pneumolysin (Ply) is a key Streptococcus pneumoniae virulence factor. Researchers found genetic diversity in Ply, which is crucial for developing effective pneumococcal vaccines.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pneumolysin (Ply) is a significant virulence factor produced by all Streptococcus pneumoniae strains.
- Ply toxoids are being evaluated as potential vaccine candidates against pneumococcal infections.
Purpose of the Study:
- To investigate the genetic diversity of pneumolysin (Ply) in nasopharyngeal isolates of Streptococcus pneumoniae.
- To assess the implications of Ply diversity for the development of Ply-based vaccines.
Main Methods:
- Characterization of 194 nasopharyngeal pneumococcal isolates using serotyping and multilocus sequence typing (MLST).
- Identification and analysis of pneumolysin (Ply) protein alleles through sequencing.
Main Results:
- Eight distinct Ply protein alleles were identified among the isolates, with four being novel.
- Novel Ply alleles exhibited variations at 10 amino acid positions.
- A strong correlation was observed between Ply protein alleles and MLST types.
Conclusions:
- Significant genetic diversity exists within the pneumolysin protein among Streptococcus pneumoniae.
- The identified Ply variants and their correlation with MLST necessitate consideration in the design of future pneumococcal vaccines.
- Amino acid variations in Ply may impact the immunogenicity of vaccines, influencing their efficacy.
Abstract:
Pneumolysin (Ply) is a major virulence factor of Streptococcus pneumoniae and is produced by all known clinical isolates of pneumococci. Pneumolysin toxoids are being considered as vaccine candidates. We investigated the diversity of pneumolysin among 194 nasopharyngeal pneumococci characterized by serotyping and multilocus sequence typing (MLST). Eight Ply protein alleles were identified, four of which were novel. The 4 novel alleles varied at 10 different amino acid positions, from a total of 147, 3 of these substitutions have been previously reported in different combinations. The protein allele correlated closely with MLST. It is critical that the presence of pneumolysin variants is considered with regards to the potential use of Ply in future vaccine formulations, as variation in Ply amino acid sequence may influence the immunogenicity of vaccines based on the presence of an individual Ply allele.
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