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.
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References
(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
Falkow S (1988) Molecular Koch's postulates applied to microbial pathogenicity. Rev Infect Dis 10(Suppl 2):S274–S276
Sarkar S, Heise MT (2019) Mouse models as resources for studying infectious diseases. Clin Ther 41(10):1912–1922
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)
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
Reglinski M, Sriskandan S (2014) The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis. Virulence 5(1):127–136
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
Barnett TC, Bowen AC, Carapetis JR (2018) The fall and rise of group A Streptococcus diseases. Epidemiol Infect 147:1–6
Brosnahan AJ (2016) Animal models used to study Superantigen-mediated diseases. Methods Mol Biol 1396:1–17
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
Gogos A, Federle MJ (2019) Modeling Streptococcus pyogenes pharyngeal colonization in the mouse. Front Cell Infect Microbiol 9:137
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
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
Saralahti A, Ramet M (2015) Zebrafish and streptococcal infections. Scand J Immunol 82(3):174–183
Stevens DL, Bryant AE (2017) Necrotizing soft-tissue infections. N Engl J Med 377(23):2253–2265
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
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
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
Adams EM, Gudmundsson S, Yocum DE, Haselby RC, Craig WA, Sundstrom WR (1985) Streptococcal myositis. Arch Intern Med 145(6):1020–1023
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
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
Dufel S, Martino M (2006) Simple cellulitis or a more serious infection? J Fam Pract 55(5):396–400
Levine EG, Manders SM (2005) Life-threatening necrotizing fasciitis. Clin Dermatol 23(2):144–147
Bellapianta JM, Ljungquist K, Tobin E, Uhl R (2009) Necrotizing fasciitis. J Am Acad Orthop Surg 17(3):174–182
Fugitt JB, Puckett ML, Quigley MM, Kerr SM (2004) Necrotizing fasciitis. Radiographics 24(5):1472–1476
Fieber C, Kovarik P (2014) Responses of innate immune cells to group a streptococcus. Front Cell Infect Microbiol 4:140
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
Barker FG, Leppard BJ, Seal DV (1987) Streptococcal necrotising fasciitis: comparison between histological and clinical features. J Clin Pathol 40(3):335–341
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
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
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
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
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
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
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
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
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
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
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
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
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
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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
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DOI: https://doi.org/10.1007/978-1-0716-1971-1_16
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