To be capsulated or not be capsulated: that is the GAS question

  • Roberta CretiEmail author
  • Giovanni Gherardi
  • Monica Imperi
Letter to the Editor

To the Editor,

The capsule of Streptococcus pyogenes (Group A Streptococcus, GAS) is composed by hyaluronic acid, the same component of the extracellular matrix of higher animals, humans included. Its synthesis as a linear polymer of N-acetylglucosamine and glucuronic acid is mediated by three enzymes whose genes (hasA, hasB, and hasC) are clustered in an operon [1, 2].

The most relevant is hasA gene, encoding a membrane-associated enzyme, hyaluronan synthase, that promotes the formation of the hyaluronic acid polymer from the nucleotide sugar precursors. The hasA gene is 1260 nucleotides long, coding for a 420 aminoacids protein. According to transcriptional studies [3], the start codon is a GTG triplet; nevertheless, many nucleotide entries identified in-frame ATG as the first codon, either upstream or downstream the GTG triplet, reporting longer or shorter deduced aminoacid sequences.

The hasABC operon is conserved among GAS strains but it is known that there are capsule-negative emm...


Supplementary material

10096_2019_3677_MOESM1_ESM.xlsx (87 kb)
Table 1 List of completed reference genomes displayed as BlastN search results. The nonsense nucleotide point mutations are in red; the non-synonymous mutations are in black; the neutral nucleotide substitutions in green (XLSX 86 kb)


  1. 1.
    Wessels MR (2016) Cell wall and surface molecules: capsule. In: Ferretti JJ, Stevens DL, Fischetti VA (eds) Streptococcus pyogenes : basic biology to clinical manifestations [internet]. University of Oklahoma Health Sciences Center, Oklahoma City (OK) Available from Google Scholar
  2. 2.
    Wessels MR (2019) Capsular polysaccharide of group a Streptococcus. Microbiol Spectr 7:1. CrossRefGoogle Scholar
  3. 3.
    Falaleeva M, Zurek OW, Watkins RL et al (2014) Transcription of the Streptococcus pyogenes hyaluronic acid capsule biosynthesis operon is regulated by previously unknown upstream elements. Infect Immun 82:5293–5307CrossRefGoogle Scholar
  4. 4.
    Flores AR, Jewell BE, Fittipaldi N, Beres SB, Musser JM (2012) Human disease isolates of serotype m4 and m22 group a streptococcus lack genes required for hyaluronic acid capsule biosynthesis. MBio 3:e00413–e00412CrossRefGoogle Scholar
  5. 5.
    Zhu L, Olsen RJ, Nasser W, de la Riva Morales I, Musser JM (2015) Trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of emm89 Streptococcus pyogenes. MBio 6:e01378–e01315. CrossRefGoogle Scholar
  6. 6.
    Efstratiou A, Sriskandan S (2015) Emergence of a new highly successful acapsular group A Streptococcus clade of genotype emm89 in the United Kingdom. MBio 6:e00622Google Scholar
  7. 7.
    Flores AR, Chase McNeil J, Shah B, Van Beneden C, Shelburne SA 3rd (2018) Capsule-negative emm types are an increasing cause of pediatric group a streptococcal infections at a large pediatric hospital in Texas. J Pediatric Infect Dis Soc 1.
  8. 8.
    Chochua S, Metcalf BJ, Li Z et al (2017) Population and whole genome sequence based characterization of invasive group a streptococci recovered in the United States during 2015. MBio 8:e01422–e01417. CrossRefGoogle Scholar
  9. 9.
    Davies MR, McIntyre L, Mutreja A et al (2019) Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics. Nat Genet 51:1035–1043. CrossRefGoogle Scholar
  10. 10.
    Stollerman GH (2001) Rheumatic fever in the 21st century. Clin Infect Dis 33:806–814CrossRefGoogle Scholar
  11. 11.
    Stollerman GH, Dale JB (2008) The importance of the group a streptococcus capsule in the pathogenesis of human infections: a historical perspective. Clin Infect Dis 46:1038–1045. CrossRefGoogle Scholar
  12. 12.
    Dale JB, Washburn RG, Marques MB, Wessels MR (1996) Hyaluronate capsule and surface M protein in resistance to opsonization of group A streptococci. Infect Immun 64:1495–1501Google Scholar
  13. 13.
    Cywes C, Wessels MR (2001) Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Nature 414:648–652CrossRefGoogle Scholar
  14. 14.
    van de Rijn I (1983) Streptococcal hyaluronic acid: proposed mechanisms of degradation and loss of synthesis during stationary phase. J Bacteriol 156:1059–1065Google Scholar
  15. 15.
    Crater DL, van de Rijn I (1995) Hyaluronic acid synthesis operon (has) expression in group A streptococci. J Biol Chem 270:18452–18458CrossRefGoogle Scholar
  16. 16.
    Flores AR, Jewell BE, Olsen RJ et al (2014) Asymptomatic carriage of group A streptococcus is associated with elimination of capsule production. Infect Immun 82:3958–3967CrossRefGoogle Scholar
  17. 17.
    Henningham A, Yamaguchi M, Aziz RK et al (2014) Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus. J Biol Chem 289:32303–33215CrossRefGoogle Scholar
  18. 18.
    Hynes W, Johnson C, Stokes M (2009) A single nucleotide mutation results in loss of enzymatic activity in the hyaluronate lyase gene of Streptococcus pyogenes. Microb Pathog 47:308–313CrossRefGoogle Scholar
  19. 19.
    Nasser W, de la Riva Morales I, Musser JM (2015) Trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of emm89 Streptococcus pyogenes. MBio 6:e01378-15CrossRefGoogle Scholar
  20. 20.
    Galloway-Peña J, DebRoy S, Brumlow C et al (2018) Hypervirulent group A Streptococcus emergence in an acaspular background is associated with marked remodeling of the bacterial cell surface. PLoS One 13(12):e0207897. CrossRefGoogle Scholar
  21. 21.
    Bernard PE, Kachroo P, Zhu L et al (2018) RocA has serotype-specific gene regulatory and pathogenesis activities in serotype M28 group A Streptococcus. Infect Immun 86(11):e00467-18. CrossRefGoogle Scholar
  22. 22.
    Bernard PE, Kachroo P, Eraso JM et al (2019) Polymorphisms in RocA Contribute to the Molecular Pathogenesis of Serotype M28 Group A Streptococcus. Am J Pathol.
  23. 23.
    Kachroo P, Eraso JM, Beres SB et al (2019) Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis. Nat Genet 51:548–559CrossRefGoogle Scholar
  24. 24.
    Matysik A, Kline KA (2019) Streptococcus pyogenes capsule promotes microcolony-independent biofilm formation. J Bacteriol.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Infectious DiseasesIstituto Superiore di SanitàRomeItaly
  2. 2.University Campus Bio-MedicoRomeItaly

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