Skip to main content
Log in

Superantigen SpeA attenuates the biofilm forming capacity of Streptococcus pyogenes

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Beta haemolytic Group A streptococcus (GAS) or Streptococcus pyogenes are strict human pathogens responsible for mild to severe fatal invasive infections. Even with enormous number of reports exploring the role of S. pyogenes exotoxins in its pathogenesis, inadequate knowledge on the biofilm process and the potential role of exotoxins in bacterial dissemination from matured biofilms has been a hindrance in development of effective and targeted treatments. Therefore, the present study was aimed in investigating the uncharted role of these exotoxins in biofilm process. Through our study the putative role of ciaRH in the SpeA dependent ablation of biofilm formation could be speculated and thus helping in bacterial dissemination. The seed-dispersal effect of SpeA was time and concentration dependent and seen to be consistent within various streptococcal species. Transcriptome analysis of SpeA treated S. pyogenes biofilms revealed the involvement of many transcriptional regulators (ciaRH) and response genes (luxS, shr, shp, SPy_0572), hinting towards specific mechanisms underlying the dispersal effect by SpeA. This finding opens up a discussion towards understanding a new mechanism involved in the pathogenesis of Streptococcus pyogenes and might help in understanding the bacterial infections in a better way.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akiyama, H., Morizane, S., Yamasaki, O., Oono, T., and Iwatsuki, K. 2003. Assessment of Streptococcus pyogenes microcolony formation in infected skin by confocal laser scanning microscopy. J. Dermatol. Sci. 32, 193–199.

    Article  PubMed  Google Scholar 

  • Andrews, S. 2010. FastQC a quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (Accessed on May 26, 2017).

  • Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., et al. 2000. Gene ontology: A tool for the unification of biology. Nat. Genet. 25, 25–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babbar, A., Bruun, T., Hyldegaard, O., Nekludov, M., Arnell, P., INFECT Study Group, Pieper, D.H., and Itzek, A. 2018. Pivotal role of preexisting pathogen-specific antibodies in the development of necrotizing soft-tissue infections. J. Infect. Dis. 218, 44–52.

    Article  CAS  PubMed  Google Scholar 

  • Baldassarri, L., Creti, R., Recchia, S., Imperi, M., Facinelli, B., Giovanetti, E., Pataracchia, M., Alfarone, G., and Orefici, G. 2006. Therapeutic failures of antibiotics used to treat macrolide-susceptible Streptococcus pyogenes infections may be due to biofilm formation. J. Clin. Microbiol. 44, 2721–2727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bankevich, A., Nurk, S., Antipov, D., Gurevich, A.A., Dvorkin, M., Kulikov, A.S., Lesin, V.M., Nikolenko, S.I., Pham, S., Prjibelski, A.D., et al. 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 19, 455–477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Billingslea, R.T. 2004. Genetic analysis of the putative streptolysin O regulator from Streptococcus pyogenes. Langston University, USA.

    Google Scholar 

  • Buffalo, V. 2011. Scythe. https://github.com/vsbuffalo/scythe (Accessed on Jun. 15, 2017).

    Google Scholar 

  • Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. 2009. BLAST+: architecture and applications. BMC Bioinformatics 10, 421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho, K.H. and Caparon, M.G. 2005. Patterns of virulence gene expression differ between biofilm and tissue communities of Streptococcus pyogenes. Mol. Microbiol. 57, 1545–1556.

    Article  CAS  PubMed  Google Scholar 

  • Conesa, A., Götz, S., García-Gómez, J.M., Terol, J., Talón, M., and Robles, M. 2005. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics 21, 3674–3676.

    Article  CAS  PubMed  Google Scholar 

  • Consortium, T.U. 2010. The universal protein resource (UniProt) in 2010. Nucleic Acids Res. 38, D142–148.

    Article  CAS  Google Scholar 

  • Courtney, H.S., Ofek, I., Penfound, T., Nizet, V., Pence, M.A., Kreikemeyer, B., Podbielski, A., Podbielbski, A., Hasty, D.L., and Dale, J.B. 2009. Relationship between expression of the family of M proteins and lipoteichoic acid to hydrophobicity and biofilm formation in Streptococcus pyogenes. PLoS One 4, e4166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunningham, M.W. 2000. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13, 470–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., and Gingeras, T.R. 2013. STAR: ultra-fast universal RNA-seq aligner. Bioinformatics 29, 15–21.

    Article  CAS  PubMed  Google Scholar 

  • Doern, C.D., Roberts, A.L., Hong, W., Nelson, J., Lukomski, S., Swords, W.E., and Reid, S.D. 2009. Biofilm formation by group A Streptococcus: A role for the streptococcal regulator of virulence (Srv) and streptococcal cysteine protease (SpeB). Microbiology 155, 46–52.

    Article  CAS  PubMed  Google Scholar 

  • Echenique, J.R., Chapuy-Regaud, S., and Trombe, M.C. 2002. Competence regulation by oxygen in Streptococcus pneumoniae: involvement of ciaRH and comCDE. Mol. Microbiol. 36, 688–696.

    Article  Google Scholar 

  • Fiedler, T., Köller, T., and Kreikemeyer, B. 2015. Streptococcus pyogenes biofilms-formation, biology, and clinical relevance. Front. Cell. Infect. Microbiol. 5, 15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finn, R.D., Tate, J., Mistry, J., Coggill, P.C., Sammut, S.J.J., Hotz, H.R.R., Ceric, G., Forslund, K., Eddy, S.R., Sonnhammer, E.L., et al. 2008. The Pfam protein families database. Nucleic Acids Res. 36, D281–D288.

    Article  CAS  PubMed  Google Scholar 

  • Halfmann, A., Schnorpfeil, A., Müller, M., Marx, P., Günzler, U., Hakenbeck, R., and Brückner, R. 2011. Activity of the two-component regulatory system CiaRH in Streptococcus pneumoniae R6. J. Mol. Microbiol. Biotechnol. 20, 96–104.

    Article  CAS  PubMed  Google Scholar 

  • Joshi, N.A. and Fass, J.N. 2011. Sickle: A sliding-window, adaptive, quality-based trimming tool for FastQ files (Version 1.33) [Software].

    Google Scholar 

  • Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., and Tanabe, M. 2014. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 42, D199–D205.

    Article  CAS  PubMed  Google Scholar 

  • Kaplan, J.B. 2010. Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses. J. Dent. Res. 89, 205–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan, J.B., Ragunath, C., Ramasubbu, N., and Fine, D.H. 2003. Detachment of Actinobacillus actinomycetemcomitans biofilm cells by an endogenous beta-hexosaminidase activity. J. Bacteriol. 185, 4693–4698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazmi, S.U., Kansal, R., Aziz, R.K., Hooshdaran, M., Norrby-Teglund, A., Low, D.E., Halim, A.B., and Kotb, M. 2001. Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group A streptococcal isolates in vivo. Infect. Immun. 69, 4988–4995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lembke, C., Podbielski, A., Hidalgo-Grass, C., Jonas, L., Hanski, E., and Kreikemeyer, B. 2006. Characterization of biofilm formation by clinically relevant serotypes of group A streptococci. Appl. Environ. Microbiol. 72, 2864–2875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Love, M.I., Huber, W., and Anders, S. 2014. Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. Genome Biol. 15, 550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makarova, K.S., Sorokin, A.V., Novichkov, P.S., Wolf, Y.I., and Koonin, E.V. 2007. Clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea. Biol. Direct 2, 33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manetti, A.G.O., Zingaretti, C., Falugi, F., Capo, S., Bombaci, M., Bagnoli, F., Gambellini, G., Bensi, G., Mora, M., Edwards, A.M., et al. 2007. Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation. Mol. Microbiol. 64, 968–983.

    Article  CAS  PubMed  Google Scholar 

  • Mascher, T., Heintz, M., Zähner, D., Merai, M., and Hakenbeck, R. 2006. The CiaRH system of Streptococcus pneumoniae prevents lysis during stress induced by treatment with cell wall inhibitors and by mutations in pbp2x involved in beta-lactam resistance. J. Bacteriol. 188, 1959–1968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L., and Wold, B. 2008. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5, 621–628.

    Article  CAS  PubMed  Google Scholar 

  • Nakata, M., Köller, T., Moritz, K., Ribardo, D., Jonas, L., McIver, K.S., Sumitomo, T., Terao, Y., Kawabata, S., Podbielski, A., et al. 2009. Mode of expression and functional characterization of FCT-3 pilus region-encoded proteins in Streptococcus pyogenes serotype M49. Infect. Immun. 77, 32–44.

    Article  CAS  PubMed  Google Scholar 

  • Proft, T. and Fraser, J.D. 2007. Streptococcal superantigens. Chem. Immunol. Allergy 93, 1–23.

    CAS  PubMed  Google Scholar 

  • Proft, T., Zealand, A.N., and Fraser, J.D. 2003. Bacterial superantigens. Clin. Exp. Immunol. 133, 299–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quevillon, E., Silventoinen, V., Pillai, S., Harte, N., Mulder, N., Apweiler, R., and Lopez, R. 2005. InterProScan: protein domains identifier. Nucleic Acids Res. 33, W116–W120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts, A. and Pachter, L. 2013. Streaming fragment assignment for real-time analysis of sequencing experiments. Nat. Methods 10, 71–73.

    Article  CAS  PubMed  Google Scholar 

  • Robinson, M.D., McCarthy, D.J., and Smyth, G.K. 2010. edgeR: a bio-conductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140.

    Article  CAS  PubMed  Google Scholar 

  • Sauer, K., Camper, A.K., Ehrlich, G.D., Costerton, J.W., and Davies, D.G. 2002. Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J. Bacteriol. 184, 1140–1154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seemann, T. 2014. Prokka: Rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069.

    Article  CAS  PubMed  Google Scholar 

  • Siemens, N., Chakrakodi, B., Shambat, S.M., Morgan, M., Bergsten, H., Hyldegaard, O., Skrede, S., Arnell, P., Madsen, M.B., Johansson, L., et al. 2016. Biofilm in group A streptococcal necrotizing soft tissue infections. JCI Insight 1, 1–13.

    Article  Google Scholar 

  • Song, Y., Zhang, X., Cai, M., Lv, C., Zhao, Y., Wei, D., and Zhu, H. 2018. The heme transporter HtsABC of group a Streptococcus contributes to virulence and innate immune evasion in murine skin infections. Front. Microbiol. 9, 1105.

    Article  PubMed  PubMed Central  Google Scholar 

  • Speziale, P. and Geoghegan, J.A. 2015. Biofilm formation by staphylococci and streptococci: structural, functional, and regulatory aspects and implications for pathogenesis. Front. Cell. Infect. Microbiol. 5, 31.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sugareva, V., Arlt, R., Fiedler, T., Riani, C., Podbielski, A., and Kreikemeyer, B. 2010. Serotype- and strain- dependent contribution of the sensor kinase CovS of the CovRS two-component system to Streptococcus pyogenes pathogenesis. BMC Microbiol. 10, 34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodbury, R.L., Wang, X., and Moran, C.P. 2006. Sigma X induces competence gene expression in Streptococcus pyogenes. Res. Microbiol. 157, 851–856.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research project has been supported by the European Union Seventh Framework Program (FP7/2013-2017) project INFECT under grant agreement no. 305340.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anshu Babbar.

Additional information

Supplemental material for this article may be found at http://www.springerlink.com/content/120956.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Babbar, A., Barrantes, I., Pieper, D.H. et al. Superantigen SpeA attenuates the biofilm forming capacity of Streptococcus pyogenes. J Microbiol. 57, 626–636 (2019). https://doi.org/10.1007/s12275-019-8648-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-019-8648-z

Keywords

Navigation