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Exposure to Acyl Homoserine Lactone Enhances Survival of Streptococcus pyogenes in Murine Macrophages

  • Host Microbe Interactions
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Abstract

Streptococcus pyogenes is an opportunistic pathogen causing infections of the skin and upper respiratory tract of the human host. Due to the polymicrobial community present in the human host, S. pyogenes comes across several interspecies signalling molecules. Among these molecules, N-(3-oxododecanoyl)-l-homoserine lactone (Oxo-C12) modulates the morphology, thereby enhancing virulence characteristics of S. pyogenes. After the initial attachment of the bacteria to the host cell, the pathogen needs to invade the host immune system for a successful infection to occur. The host immune system is activated upon infection, where macrophages engulf the pathogen, thereby killing the bacteria. However, S. pyogenes have evolved various strategies to evade the host immune response. In this study, we investigate the role of Oxo-C12 in enhancing the survival of S. pyogenes M3 in murine macrophages. The observed Oxo-C12-mediated increased survival in murine macrophages was through increased lysozyme and acid stress resistance. Moreover, Oxo-C12 increased the survival of S. pyogenes in normal human serum. Thus, understanding the role of interspecies signalling in enhancing the survival strategies of S. pyogenes in the host will further help fill the gap for therapeutics development.

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References

  1. Carapetis JR, Steer AC, Mulholland EK, Weber M (2005) The global burden of group A streptococcal diseases. Lancet Infect Dis 5(11):685–694

    Article  Google Scholar 

  2. Steer AC, Danchin MH, Carapetis JR (2007) Group A streptococcal infections in children. J Paediatr Child Health 43(4):203–213

    Article  Google Scholar 

  3. Beres SB, Sylva GL, Barbian KD, Lei B, Hoff JS, Mammarella ND, ... Musser JM (2002) Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proceedings of the national academy of sciences, 99(15), 10078-10083

  4. Cao TN, Liu Z, Cao TH, Pflughoeft KJ, Treviño J, Danger JL, ... & Sumby P (2014) Natural disruption of two regulatory networks in serotype M3 group A Streptococcus isolates contributes to the virulence factor profile of this hypervirulent serotype. Infection and immunity, 82(5), 1744-1754

  5. Miller EW, Danger JL, Ramalinga AB, Horstmann N, Shelburne SA, Sumby P (2015) Regulatory rewiring confers serotype-specific hyper-virulence in the human pathogen group A Streptococcus. Mol Microbiol 98(3):473–489

    Article  CAS  Google Scholar 

  6. Banerji R, Kanojiya P, Saroj SD (2020) Role of interspecies bacterial communication in the virulence of pathogenic bacteria. Crit Rev Microbiol 46(2):136–146

    Article  Google Scholar 

  7. Saroj SD, Holmer L, Berengueras JM, Jonsson AB (2017) Inhibitory role of acyl homoserine lactones in hemolytic activity and viability of Streptococcus pyogenes M6 S165. Sci Rep 7(1):1–11

    Article  Google Scholar 

  8. Banerji R, Saroj SD (2021) Interspecies signaling affects virulence related morphological characteristics of Streptococcus pyogenes M3. FEMS Microbiol Lett 368(13):fnab079. https://doi.org/10.1093/femsle/fnab079

  9. Spinaci C, Magi G, Varaldo PE, Facinelli B (2006) Persistence of erythromycin-resistant group A streptococci in cultured respiratory cells. Pediatr Infect Dis J 25(10):880–883

    Article  Google Scholar 

  10. Goldmann O, Rohde M, Chhatwal GS, Medina E (2004) Role of macrophages in host resistance to group A streptococci. Infect Immun 72(5):2956–2963

    Article  CAS  Google Scholar 

  11. Fieber C, Kovarik P (2014) Responses of innate immune cells to group A Streptococcus. Front Cell Infect Microbiol 4:140

    Article  Google Scholar 

  12. Dinkla K, Sastalla I, Godehardt AW, Janze N, Chhatwal GS, Rohde M, Medina E (2007) Upregulation of capsule enables Streptococcus pyogenes to evade immune recognition by antigen-specific antibodies directed to the G-related α2-macroglobulin-binding protein GRAB located on the bacterial surface. Microbes Infect 9(8):922–931

    Article  CAS  Google Scholar 

  13. Timmer AM, Timmer JC, Pence MA, Hsu LC, Ghochani M, Frey TG, ... Nizet V (2009) Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis. J Biol Chem, 284(2), 862-871

  14. Wierzbicki IH, Campeau A, Dehaini D, Holay M, Wei X, Greene T, ... Gonzalez DJ (2019) Group A streptococcal S protein utilizes red blood cells as immune camouflage and is a critical determinant for immune evasion. Cell Rep, 29(10), 2979-2989

  15. Sigurlásdóttir S, Saroj SD, Eriksson OS, Eriksson J, Jonsson AB (2018) Quantification of Neisseria meningitidis adherence to human epithelial cells by colony counting. Bio-Protoc 8(3):e2709–e2709

    Article  Google Scholar 

  16. Ricci S, Janulczyk R, Björck L (2002) The regulator PerR is involved in oxidative stress response and iron homeostasis and is necessary for full virulence of Streptococcus pyogenes. Infect Immun 70(9):4968–4976

    Article  CAS  Google Scholar 

  17. Amano F, Noda T (1995) Improved detection of nitric oxide radical (NO•) production in an activated macrophage culture with a radical scavenger, carboxy PTIO, and Griess reagent. FEBS Lett 368(3):425–428

    Article  CAS  Google Scholar 

  18. Blaschke U, Beineke A, Klemens J, Medina E, Goldmann O (2017) Induction of cyclooxygenase 2 by Streptococcus pyogenes is mediated by cytolysins. J Innate Immun 9(6):587–597

    Article  CAS  Google Scholar 

  19. Cusumano ZT, Watson ME Jr, Caparon MG (2014) Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity. Infect Immun 82(1):233–242

    Article  Google Scholar 

  20. Goldmann O, Hertzén E, Hecht A, Schmidt H, Lehne S, Norrby-Teglund A, Medina E (2010) Inducible cyclooxygenase released prostaglandin E2 modulates the severity of infection caused by Streptococcus pyogenes. J Immunol 185(4):2372–2381

    Article  CAS  Google Scholar 

  21. Agard M, Asakrah S, Morici LA (2013) PGE2 suppression of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 3:45

    Article  CAS  Google Scholar 

  22. Cusumano ZT, Caparon MG (2015) Citrulline protects Streptococcus pyogenes from acid stress using the arginine deiminase pathway and the F1Fo-ATPase. J Bacteriol 197(7):1288–1296

    Article  CAS  Google Scholar 

  23. Kristian SA, Datta V, Weidenmaier C, Kansal R, Fedtke I, Peschel A, ... Nizet V (2005) D-alanylation of teichoic acids promotes group A Streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. J Bacteriol, 187(19), 6719-6725

  24. Honda-Ogawa M, Sumitomo T, Mori Y, Hamd DT, Ogawa T, Yamaguchi M, ... Kawabata S (2017) Streptococcus pyogenes endopeptidase O contributes to evasion from complement-mediated bacteriolysis via binding to human complement factor C1q. J Biol Chem, 292(10), 4244-4254

  25. Davis KM, Weiser JN (2011) Modifications to the peptidoglycan backbone help bacteria to establish infection. Infect Immun 79(2):562–570

    Article  CAS  Google Scholar 

  26. Bastiat-Sempe B, Love JF, Lomayesva N, Wessels MR (2014) Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group A Streptococcus survival in macrophages. MBio 5(5):e01690-e1714

    Article  CAS  Google Scholar 

  27. Goldmann O, Sastalla I, Wos-Oxley M, Rohde M, Medina E (2009) Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway. Cell Microbiol 11(1):138–155

    Article  CAS  Google Scholar 

  28. Sierig G, Cywes C, Wessels MR, Ashbaugh CD (2003) Cytotoxic effects of streptolysin O and streptolysin S enhance the virulence of poorly encapsulated group A streptococci. Infect Immun 71(1):446–455

    Article  CAS  Google Scholar 

  29. Medina E, Rohde M, Chhatwal GS (2003) Intracellular survival of Streptococcus pyogenes in polymorphonuclear cells results in increased bacterial virulence. Infect Immun 71(9):5376–5380

    Article  CAS  Google Scholar 

  30. Håkansson A, Bentley CC, Shakhnovic EA, Wessels MR (2005) Cytolysin-dependent evasion of lysosomal killing. Proc Natl Acad Sci 102(14):5192–5197

    Article  Google Scholar 

  31. O’Neill AM, Thurston TL, Holden DW (2016) Cytosolic replication of group A Streptococcus in human macrophages. MBio 7(2):e00020-e116

    Article  Google Scholar 

  32. Gogos A, Jimenez JC, Chang JC, Wilkening RV, Federle MJ (2018) A quorum sensing-regulated protein binds cell wall components and enhances lysozyme resistance in Streptococcus pyogenes. J Bacteriol 200(11):e00701-e717

    Article  CAS  Google Scholar 

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Acknowledgements

R. B. is supported by the senior research fellowship program of Symbiosis International (Deemed University).

Funding

The work was supported by the Ramalingaswami fellowship program of the Department of Biotechnology, India, under grant BT/RLF/Re-entry/41/2015.

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S. D. conceptualized the idea and designed the experiments. R. B. performed the experiments and prepared the manuscript. R. B. and S. D. finalized the manuscript.

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Correspondence to Sunil D. Saroj.

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The authors declare no competing interests.

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Banerji, R., Saroj, S.D. Exposure to Acyl Homoserine Lactone Enhances Survival of Streptococcus pyogenes in Murine Macrophages. Microb Ecol 84, 1256–1263 (2022). https://doi.org/10.1007/s00248-021-01926-1

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  • DOI: https://doi.org/10.1007/s00248-021-01926-1

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