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Updated: Apr 23, 2026

Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
Published on: September 11, 2020
Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce
Yunjuan Bao1, Zhong Liang2, Claire Booyjzsen2
1W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Abstract:
The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF(-)) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ΦM23ND.1 to ΦM23ND.4, harboring genes encoding streptococcal superantigen (ssa), streptococcal pyrogenic exotoxins (speC, speH, and speI), and DNases (spd1 and spd3), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The covS sensor in M23ND was identified as a pseudogene, resulting in the attenuation of speB function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (mga), M protein (emm23), C5a peptidase (scpA), fibronectin-binding proteins (sfbI and fbp54), streptolysin O (slo), hyaluronic acid capsule (hasA), streptokinase (ska), and DNases (spd and spd3), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors.
Insights
The genome of invasive Streptococcus pyogenes M23ND reveals unique rearrangements and prophage integrations. These genetic factors contribute to its high pathogenicity and ability to evade host immune responses.
Area of Science:
- Microbiology
- Genomics
- Pathogenesis
Background:
- Group A Streptococcus (GAS) causes invasive infections.
- Understanding GAS virulence factors is crucial for developing treatments.
Purpose of the Study:
- To sequence and analyze the genome of a pathogenic emm23 strain (M23ND).
- To identify genetic factors contributing to its virulence.
Main Methods:
- Whole-genome sequencing of M23ND.
- Comparative genomic analysis with other GAS strains.
- PCR verification of virulence gene expression.
Main Results:
- M23ND genome has unique large-scale rearrangements and four prophage elements.
- Acquired prophages encode superantigens and DNases.
- Mutations in covS lead to increased expression of key virulence genes like mga and emm23.
Conclusions:
- M23ND's high pathogenicity results from a combination of genetic factors.
- Prophage integrations and genomic rearrangements enhance virulence.
- Altered gene expression, particularly of chromosomal factors, contributes to host immune evasion.
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