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Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
Published on: September 11, 2020
Differences in genotype and virulence among four multidrug-resistant Streptococcus pneumoniae isolates belonging to
N Luisa Hiller1, Rory A Eutsey, Evan Powell
1Allegheny General Hospital, Allegheny-Singer Research Institute, Center for Genomic Sciences, Pittsburgh, Pennsylvania, United States of America.
Abstract:
We report on the comparative genomics and characterization of the virulence phenotypes of four S. pneumoniae strains that belong to the multidrug resistant clone PMEN1 (Spain(23F) ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinants.
Insights
Comparative genomics revealed high conservation within the multidrug-resistant PMEN1 clone of Streptococcus pneumoniae. Despite genomic similarity, variations in virulence were observed, highlighting small genetic changes
Area of Science:
- Genomics
- Microbiology
- Infectious Diseases
Background:
- The PMEN1 (Spain(23F) ST81) clone of Streptococcus pneumoniae is a significant multidrug-resistant lineage.
- Understanding genomic diversity and virulence factors within this clone is crucial for combating pneumococcal infections.
- Previous studies have not fully characterized the genomic variations and their impact on virulence within the PMEN1 clone.
Purpose of the Study:
- To perform comparative genomics on four multidrug-resistant PMEN1 Streptococcus pneumoniae strains.
- To characterize the virulence phenotypes of these strains using a high-resolution animal model.
- To identify specific genomic regions and variations associated with differences in pathogenicity.
Main Methods:
- Whole-genome sequencing of four PMEN1 strains (isolated 1984-1996 from Spain, Portugal, and USA).
- Comparative genomic analysis against 47 diverse Streptococcus pneumoniae isolates to identify gene content and allelic variations.
- Virulence phenotyping using a high-resolution chinchilla infection model.
Main Results:
- The four PMEN1 strains exhibited high genomic conservation compared to other pneumococcal types.
- Genomic differences were concentrated in 18 specific regions, including capsule genes, bacteriocins, antibiotic resistance, and cell wall proteins.
- Despite genomic similarity, significant variations in virulence were detected in the chinchilla model, indicating small genetic changes impact pathogenicity.
Conclusions:
- The PMEN1 clone demonstrates remarkable genomic stability, with variations localized to specific functional regions.
- Even minor genomic or allelic variations within the PMEN1 lineage can lead to substantial differences in virulence.
- These strains provide a valuable resource for identifying novel virulence determinants and understanding pneumococcal pathogenesis.
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