title: Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity.
abstract: The genome of an invasive skin-tropic strain (AP53) of serotype M53 group A Streptococcus pyogenes (GAS) is composed of a circular chromosome of 1,860,554 bp and carries genetic markers for infection at skin locales, viz, emm gene family pattern D and FCT type 3. Through genome-scale comparisons of AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal a potential genetic basis for skin tropism. The genome of AP53 differed by ∼30 point mutations from a noninvasive pattern D serotype M53 strain (Alab49), 4 of which are located in virulence genes. One pseudogene, yielding an inactive sensor kinase (CovS(-)) of the two-component transcriptional regulator CovRS, a major determinant for invasiveness, severely attenuated the expression of the secreted cysteine protease SpeB and enhanced the expression of the hyaluronic acid capsule compared to the isogenic noninvasive AP53/CovS(+) strain. The collagen-binding protein transcript sclB differed in the number of 5'-pentanucleotide repeats in the signal peptides of AP53 and Alab49 (9 versus 15), translating into different lengths of their signal peptides, which nonetheless maintained a full-length translatable coding frame. Furthermore, GAS strain AP53 acquired two phages that are absent in Alab49. One such phage (ΦAP53.2) contains the known virulence factor superantigen exotoxin gene tandem speK-slaA Overall, we conclude that this bacterium has evolved in multiple ways, including mutational variations of regulatory genes, short-tandem-repeat polymorphisms, large-scale genomic alterations, and acquisition of phages, all of which may be involved in shaping the adaptation of GAS in specific infectious environments and contribute to its enhanced virulence.
  
  
  
  Infectious strains of S. pyogenes (GAS) are classified by their serotypes, relating to the surface M protein, the emm-like subfamily pattern, and their tropicity toward the nasopharynx and/or skin. It is generally agreed that M proteins from pattern D strains, which also directly bind human host plasminogen, are skin tropic. We have sequenced and characterized the genome of an invasive pattern D GAS strain (AP53) in comparison to a very similar strain (Alab49) that is noninvasive and developed a genomic rationale as to possible reasons for the skin tropicity of these two strains and the greater invasiveness of AP53.
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Yun-Juan
authors.initials: YJ
authors.lastname: Bao
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA 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, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mayfield
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Donahue
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Katelyn E
authors.initials: KE
authors.lastname: Carothers
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA 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, University of Notre Dame, Notre Dame, Indiana, USA 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: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA 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: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D012871:Skin Diseases / Q000382:microbiology*; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors