Murine Soft Tissue Infection Model to Study Group A Streptococcus (GAS) Pathogenesis in Necrotizing Fasciitis

  • Protocol
  • First Online:
Bacterial Virulence

Abstract

Group A streptococcus (GAS) necrotizing fasciitis (NF) causes high morbidity and mortality despite prompt intravenous administration of antibiotics, surgical soft-tissue debridement, and supportive treatment in the intensive care unit. Since there is no effective vaccine against GAS infections, a comprehensive understanding of NF pathogenesis is required to design more efficient treatments. To increase our understanding of NF pathogenesis, we need a reliable animal model that mirrors, at least in part, the infectious process in humans. This chapter describes a reliable murine model of human NF that mimics the histopathology observed in humans, namely the destruction of soft tissue, a paucity of infiltrating neutrophils, and the presence of many gram-positive cocci at the center of the infection.

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. (1882) Koch. [Die Atiologie der Tuberculose. Facsimile of the original contribution by Robert Koch in "Berliner Klinische Wochenschrift" 10 April 1882]. Fortschr Med 100(12):539

    Google Scholar 

  2. Falkow S (1988) Molecular Koch's postulates applied to microbial pathogenicity. Rev Infect Dis 10(Suppl 2):S274–S276

    Article  Google Scholar 

  3. Sarkar S, Heise MT (2019) Mouse models as resources for studying infectious diseases. Clin Ther 41(10):1912–1922

    Article  CAS  Google Scholar 

  4. Watson ME Jr, Neely MN, Caparon MG (2016) Animal models of Streptococcus pyogenes infection. In: Ferretti JJ, Stevens DL, Fischetti VA (eds) Streptococcus pyogenes: basic biology to clinical manifestations. University of Oklahoma Health Sciences Center, Oklahoma City (OK)

    Google Scholar 

  5. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A et al (2014) Disease manifestations and pathogenic mechanisms of group A streptococcus. Clin Microbiol Rev 27(2):264–301

    Article  Google Scholar 

  6. Reglinski M, Sriskandan S (2014) The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis. Virulence 5(1):127–136

    Article  Google Scholar 

  7. Sun H, Ringdahl U, Homeister JW, Fay WP, Engleberg NC, Yang AY et al (2004) Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 305(5688):1283–1286

    Article  CAS  Google Scholar 

  8. Barnett TC, Bowen AC, Carapetis JR (2018) The fall and rise of group A Streptococcus diseases. Epidemiol Infect 147:1–6

    Google Scholar 

  9. Brosnahan AJ (2016) Animal models used to study Superantigen-mediated diseases. Methods Mol Biol 1396:1–17

    Article  CAS  Google Scholar 

  10. Cutforth T, DeMille MM, Agalliu I, Agalliu D (2016) CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors. Future Neurol 11(1):63–76

    Article  CAS  Google Scholar 

  11. Gogos A, Federle MJ (2019) Modeling Streptococcus pyogenes pharyngeal colonization in the mouse. Front Cell Infect Microbiol 9:137

    Article  CAS  Google Scholar 

  12. Lamb LE, Zhi X, Alam F, Pyzio M, Scudamore CL, Wiles S et al (2018) Modelling invasive group A streptococcal disease using bioluminescence. BMC Microbiol 18(1):60

    Article  CAS  Google Scholar 

  13. Rush CM, Govan BL, Sikder S, Williams NL, Ketheesan N (2014) Animal models to investigate the pathogenesis of rheumatic heart disease. Front Pediatr 2:116

    Article  Google Scholar 

  14. Saralahti A, Ramet M (2015) Zebrafish and streptococcal infections. Scand J Immunol 82(3):174–183

    Article  CAS  Google Scholar 

  15. Stevens DL, Bryant AE (2017) Necrotizing soft-tissue infections. N Engl J Med 377(23):2253–2265

    Article  Google Scholar 

  16. Audureau E, Hua C, de Prost N, Hemery F, Decousser JW, Bosc R et al (2017) Mortality of necrotizing fasciitis: relative influence of individual and hospital-level factors, a nationwide multilevel study, France, 2007-12. Br J Dermatol 177(6):1575–1582

    Article  CAS  Google Scholar 

  17. Huang KF, Hung MH, Lin YS, Lu CL, Liu C, Chen CC et al (2011) Independent predictors of mortality for necrotizing fasciitis: a retrospective analysis in a single institution. J Trauma 71(2):467–473; discussion 73

    PubMed  Google Scholar 

  18. Nelson GE, Pondo T, Toews KA, Farley MM, Lindegren ML, Lynfield R et al (2016) Epidemiology of invasive group a streptococcal infections in the United States, 2005-2012. Clin Infect Dis 63(4):478–486

    Article  Google Scholar 

  19. Adams EM, Gudmundsson S, Yocum DE, Haselby RC, Craig WA, Sundstrom WR (1985) Streptococcal myositis. Arch Intern Med 145(6):1020–1023

    Article  CAS  Google Scholar 

  20. Mehta S, McGeer A, Low DE, Hallett D, Bowman DJ, Grossman SL et al (2006) Morbidity and mortality of patients with invasive group A streptococcal infections admitted to the ICU. Chest 130(6):1679–1686

    Article  Google Scholar 

  21. Bryant AE, Bayer CR, Chen RY, Guth PH, Wallace RJ, Stevens DL (2005) Vascular dysfunction and ischemic destruction of tissue in Streptococcus pyogenes infection: the role of streptolysin O-induced platelet/neutrophil complexes. J Infect Dis 192(6):1014–1022

    Article  CAS  Google Scholar 

  22. Dufel S, Martino M (2006) Simple cellulitis or a more serious infection? J Fam Pract 55(5):396–400

    PubMed  Google Scholar 

  23. Levine EG, Manders SM (2005) Life-threatening necrotizing fasciitis. Clin Dermatol 23(2):144–147

    Article  Google Scholar 

  24. Bellapianta JM, Ljungquist K, Tobin E, Uhl R (2009) Necrotizing fasciitis. J Am Acad Orthop Surg 17(3):174–182

    Article  Google Scholar 

  25. Fugitt JB, Puckett ML, Quigley MM, Kerr SM (2004) Necrotizing fasciitis. Radiographics 24(5):1472–1476

    Article  Google Scholar 

  26. Fieber C, Kovarik P (2014) Responses of innate immune cells to group a streptococcus. Front Cell Infect Microbiol 4:140

    Article  Google Scholar 

  27. Voyich JM, Braughton KR, Sturdevant DE, Vuong C, Kobayashi SD, Porcella SF et al (2004) Engagement of the pathogen survival response used by group A streptococcus to avert destruction by innate host defense. J Immunol 173(2):1194–1201

    Article  CAS  Google Scholar 

  28. Barker FG, Leppard BJ, Seal DV (1987) Streptococcal necrotising fasciitis: comparison between histological and clinical features. J Clin Pathol 40(3):335–341

    Article  CAS  Google Scholar 

  29. Hietbrink F, Bode LG, Riddez L, Leenen LP, van Dijk MR (2016) Triple diagnostics for early detection of ambivalent necrotizing fasciitis. World J Emerg Surg 11:51

    Article  Google Scholar 

  30. Lancerotto L, Tocco I, Salmaso R, Vindigni V, Bassetto F (2012) Necrotizing fasciitis: classification, diagnosis, and management. J Trauma Acute Care Surg 72(3):560–566

    Article  Google Scholar 

  31. Bakleh M, Wold LE, Mandrekar JN, Harmsen WS, Dimashkieh HH, Baddour LM (2005) Correlation of histopathologic findings with clinical outcome in necrotizing fasciitis. Clin Infect Dis 40(3):410–414

    Article  Google Scholar 

  32. Taylor FB Jr, Bryant AE, Blick KE, Hack E, Jansen PM, Kosanke SD et al (1999) Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns. Clin Infect Dis 29(1):167–177

    Article  Google Scholar 

  33. Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn LA, Nizet V et al (2004) Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections. Lancet 363(9410):696–703

    Article  CAS  Google Scholar 

  34. Moses AE, Goldberg S, Korenman Z, Ravins M, Hanski E, Shapiro M (2002) Invasive group a streptococcal infections. Israel Emerg Infect Dis 8(4):421–426

    Article  Google Scholar 

  35. Edwards RJ, Taylor GW, Ferguson M, Murray S, Rendell N, Wrigley A et al (2005) Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes. J Infect Dis 192(5):783–790

    Article  CAS  Google Scholar 

  36. Goldblatt J, Lawrenson RA, Muir L, Dattani S, Hoffland A, Tsuchiya T et al (2019) A requirement for neutrophil Glycosaminoglycans in chemokine:receptor interactions is revealed by the streptococcal protease SpyCEP. J Immunol 202(11):3246–3255

    Article  CAS  Google Scholar 

  37. Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V et al (2006) A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues. EMBO J 25(19):4628–4637

    Article  CAS  Google Scholar 

  38. Jobichen C, Tan YC, Prabhakar MT, Nayak D, Biswas D, Pannu NS et al (2018) Structure of ScpC, a virulence protease from streptococcus pyogenes, reveals the functional domains and maturation mechanism. Biochem J 475(17):2847–2860

    Article  CAS  Google Scholar 

  39. Zingaretti C, Falugi F, Nardi-Dei V, Pietrocola G, Mariani M, Liberatori S et al (2010) Streptococcus pyogenes SpyCEP: a chemokine-inactivating protease with unique structural and biochemical features. FASEB J 24(8):2839–2848

    Article  CAS  Google Scholar 

  40. Kurupati P, Turner CE, Tziona I, Lawrenson RA, Alam FM, Nohadani M et al (2010) Chemokine-cleaving streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract. Mol Microbiol 76(6):1387–1397

    Article  CAS  Google Scholar 

  41. Zinkernagel AS, Timmer AM, Pence MA, Locke JB, Buchanan JT, Turner CE et al (2008) The IL-8 protease SpyCEP/ScpC of group a streptococcus promotes resistance to neutrophil killing. Cell Host Microbe 4(2):170–178

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Emanuel Hanski .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Ravins, M. et al. (2022). Murine Soft Tissue Infection Model to Study Group A Streptococcus (GAS) Pathogenesis in Necrotizing Fasciitis. In: Gal-Mor, O. (eds) Bacterial Virulence. Methods in Molecular Biology, vol 2427. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1971-1_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1971-1_16

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1970-4

  • Online ISBN: 978-1-0716-1971-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Navigation