title: Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence.
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.
authors.affiliation: W. 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.
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Booyjzsen
authors.affiliation: W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mayfield
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Shaun W
authors.initials: SW
authors.lastname: Lee
authors.affiliation: W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA fcastell@nd.edu.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D001422:Bacterial Adhesion; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D016133:Polymerase Chain Reaction; D039002:Prophages / Q000235:genetics; D011544:Pseudogenes; D011995:Recombination, Genetic; D065288:Serogroup; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D037521:Virulence Factors