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.
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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.
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.
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.
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.
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.
Billingslea, R.T. 2004. Genetic analysis of the putative streptolysin O regulator from Streptococcus pyogenes. Langston University, USA.
Buffalo, V. 2011. Scythe. https://github.com/vsbuffalo/scythe (Accessed on Jun. 15, 2017).
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.
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.
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.
Consortium, T.U. 2010. The universal protein resource (UniProt) in 2010. Nucleic Acids Res. 38, D142–148.
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.
Cunningham, M.W. 2000. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13, 470–511.
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.
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.
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.
Fiedler, T., Köller, T., and Kreikemeyer, B. 2015. Streptococcus pyogenes biofilms-formation, biology, and clinical relevance. Front. Cell. Infect. Microbiol. 5, 15.
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.
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.
Joshi, N.A. and Fass, J.N. 2011. Sickle: A sliding-window, adaptive, quality-based trimming tool for FastQ files (Version 1.33) [Software].
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.
Kaplan, J.B. 2010. Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses. J. Dent. Res. 89, 205–218.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Proft, T. and Fraser, J.D. 2007. Streptococcal superantigens. Chem. Immunol. Allergy 93, 1–23.
Proft, T., Zealand, A.N., and Fraser, J.D. 2003. Bacterial superantigens. Clin. Exp. Immunol. 133, 299–306.
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.
Roberts, A. and Pachter, L. 2013. Streaming fragment assignment for real-time analysis of sequencing experiments. Nat. Methods 10, 71–73.
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.
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.
Seemann, T. 2014. Prokka: Rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069.
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.
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.
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.
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.
Woodbury, R.L., Wang, X., and Moran, C.P. 2006. Sigma X induces competence gene expression in Streptococcus pyogenes. Res. Microbiol. 157, 851–856.
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This research project has been supported by the European Union Seventh Framework Program (FP7/2013-2017) project INFECT under grant agreement no. 305340.
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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
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DOI: https://doi.org/10.1007/s12275-019-8648-z