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Streptococcus pyogenes

Streptococcus pyogenes. Rebecca Walsh Smith College BIO 360 Spring 2005. Outline. History of S.pyogenes Epidemiology Biology Vaccine Development Conclusions.

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Streptococcus pyogenes

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  1. Streptococcus pyogenes Rebecca Walsh Smith College BIO 360 Spring 2005

  2. Outline • History of S.pyogenes • Epidemiology • Biology • Vaccine Development • Conclusions Title Slide image from: http://www.geo.de/GEO/fotografie/portfolio_des_monats/2001_10_portfolio_meckes/page13.html?linkref=geode_pager

  3. History • 5th century BC – Hippocrates • 1874 – Billroth • 1884 – Pasteur • Late 19th century – Rosenbach • 1919 – Brown • 1930’s – Lancefield • 1980’s/90’s http://www.mja.com.au/public/issues/177_11_021202/dec10354_fm.html http://medicine.ucsd.edu/nizetlab/streptococcipage/streptococci.html

  4. Outline • History of S.pyogenes • Epidemiology • Transmission • Frequency • Confirmation Tests • Treatment • Biology • Vaccine Development • Conclusions

  5. Transmission • Initially colonizes skin and pharynx • Person-to-person spread • Strains that cause skin infections are spread via skin contact • Strains that cause respiratory infections are spread via respiratory droplets • Less common is food or waterborne • The immunucompromised are especially susceptible http://www.cellsalive.net/photos/

  6. Frequency • In the US: • Study from 1995-1999 showed that invasive GAS infections occurred in 3.6/100,000 people annually • Upper respiratory tract infections most common in northern regions • Skin infections most frequent during summer • Internationally: • Skin infections most common in the tropics http://textbookofbacteriology.net/normalflora.html

  7. Rapid Ag detection Culture Beta-hemolysis PYRase Bacitracin Tests to Confirm Infection Beta-Hemolysis Bacitracin http://www.med.sc.edu:85/fox/streptococci.htm http://www.austin.cc.tx.us/microbugz/44a_p.html

  8. Treatment • Penicillin • Interferes with the synthesis of a peptide in the bacterial cell wall • Clindamycin • Inhibits RNA-dependent protein synthesis • Vancomycin • For people allergic to penicillin • Vaccines “Staphylococcus aureus growth is inhibited in the area surrounding the invading penicillin-secreting Penicillium mold colony.” http://www.accessexcellence.org/AE/AEC/CC/s5.html

  9. Outline • History of S.pyogenes • Epidemiology • Biology • Basic Information • Diseases • Genome • Virulence Factors • Vaccine Development • Conclusions

  10. Biology Basics • Gram-positive bacterium • Occur in pairs or short chains • Cells are 0.6-1.0 μm in diameter • Further subdivided by serotypes http://textbookofbacteriology.net/BSRP.html

  11. Diseases Pathogenesis of S.pyogenes Infections http://www.textbookofbacteriology.net/streptococcus.html

  12. Diseases Cont’d Image taken from: Batzloff, et al.

  13. Strep Throat • S.pyogenes is leading cause of uncomplicated bacterial pharyngitis and tonsillitis • Common in winter and early spring in children over age 3 • Typical symptoms: • Pus in throat • Reddened and inflamed tonsils and uvula • Tiny, reddish-brown spots at back of throat • Swollen lymph nodes and tongue • Treatment is best 48 hours after symptom onset http://www.lib.uiowa.edu/hardin/md/strepthroat.html

  14. Acute Rheumatic Fever • Inflammatory disease mediated by autoimmune mechanisms activated by GAS infection • Typically follows pharyngitis • Symptoms include migratory arthritis, chorea, and carditis • 20 million new cases annually Chest radiograph of an 8 year-old patient with acute carditis before (←) treatment, and after 4 weeks of treatment (↓) http://www.health.gov.mt/impaedcard/issue/issue11/1231/1231.htm

  15. S.pyogenes Necrotizing Fasciitis • “Flesh-eating bacteria” • 600 cases annually in US • Rapidly progressive • Any part of body can be infected • Common in abdomen, perineum, and extremities • Patients present with red skin, lesions • Untreated patients will die within 4 days http://www.aic.cuhk.edu.hk/web8/toc.htm http://catalog.nucleusinc.com/generateexhibit.php?ID=11447&ExhibitKeywordsRaw=&TL=16353&A=2

  16. S.pyogenes Genome • Approximately 1,900,000 base pairs • Has over 40 virulence-associated genes • Numerous genes involved in molecular mimicry http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=11296296

  17. Virulence Factors Known or Postulated GAS Virulence Factors in Humans • Involved in: • Antiphagocytosis • Adherence • Internalization • Invasion/spread through host tissues • Systemic toxicity Image adapted from: Bisno, et al.

  18. Virulence Factors Cont’d ◄ ► ► Image taken from: Mitchell http://www.textbookofbacteriology.net/streptococcus.html

  19. Host Response • S.pyogenes is usually an exogenous secondary invader • Skin is first line of defense • Host phagocytic system is second line of defense • Protective immunity is third line of defense Phagocyte Engulfing GAS Chain http://www.cellsalive.com/strep.htm

  20. Act to kill host cells and provoke inflammation Invasins Streptococcal pyrogenic exotoxins Extracellular Products Invasin Superantigen http://www.cco.caltech.edu/~astrid/invasin.html http://www.mgc.ac.cn/VFs/Figures/Streptococcus/superantigen.png

  21. Hyaluronic Acid Capsule • Non-antigenic • Adhesin • Prevents opsonized phagocytosis • Amount of encapsulation varies between GAS strains • Highly encapsulated strains with lots of M protein are associated with invasive GAS diseases “A Bacterial Capsule Preventing Receptors on Phagocytes from Binding to Bacterial Cell Wall” http://www.cat.cc.md.us/courses/bio141/lecguide/unit1/bacpath/capc3b.html

  22. M Protein • Major virulence factor • Composed of 3 regions: • Hypervariable (N-terminus) • Variable (A- and B-repeats) • Conserved (C-repeats) • Antigenic differences in the hypervariable region constitute the basis for the Lancefield serological classification of GAS • Over 120 types • Antibodies against one type confer no protection against others Image taken from: Bisno, et al.

  23. Complement Pathway Image taken from: Mitchell

  24. M Protein Cont’d • Involved in colonization and resistance to phagocytosis • Mediates antiphagocytic effect by inhibiting activation of alternate complement pathway • Confers resistance to phagocytosis because it acts as an adhesin • Shares sequence homology with mammalian fibrillar proteins, providing a structural basis for induction of autoimmunity following GAS infection http://www.rockefeller.edu/vaf/m.htm

  25. Outline • History of S.pyogenes • Epidemiology • Biology • Vaccine Development • Current Situation • Potential Vaccines • Conclusions

  26. Other Streptococci? Difficulties in targeting the M protein Variability Cross-Reactivity Vaccine Development http://www.montana.edu/wwwwami/523/Reading11.htm

  27. Multivalent Vaccines • Study by Dey, et al. • Surveyed GAS emm types from India • Results showed high number of types with no predominant strain • Need for multivalent vaccines • Geographic bias in distribution? Image taken from: Dey, et al.

  28. Potential Vaccines • Recombinant • Serotypic determinant approach • StreptavaxTM • Conserved region approach • Synthetic peptide http://www.auburnschl.edu/OtherInfo/immunizations.html

  29. Conclusions • Causes numerous diseases • Increasing bacterial resistance to treatment • Many virulence factors provide options for vaccine development • Currently, the M protein is our best vaccine target option, and StreptavaxTM is our best hope for a vaccine http://www.microbiology.emory.edu/scott/index_main.htm

  30. Thank you! • In appreciation for their contributions: • Dr. Christine White-Ziegler • Reviewers Jill Falk and Barbara Jennings-Spring • Individuals whose websites provided the images for this presentation http://www.smbs.buffalo.edu/wcmpi/faculty/stinson.html

  31. American Society of Clinical Pathologists. http://www.api-pt.com/pdfs/2001Bmicro.pdf. 2001. Batzloff MR, Sriprakash KS, Good MF. Vaccine development for group A Streptococcus infections and associated diseases. Current Drug Targets 2004; 5(1): 57-69. Bisno AL, Brito MO, Collins CM. Molecular basis of group A streptococcal virulence. The Lancet Infectious Diseases 2003; 3: 191-200. Centers for Disease Control and Prevention. Group A streptococcal (GAS) disease. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/groupastreptococcal_g.htm. 2003. Columbia Encyclopedia, Sixth Edition. Bacitracin. http://www.encyclopedia.com/htl/b1/bacitrac.asp. 2005. Dey N, McMillan DJ, Yarwood PJ, et al. High diversity of group A streptococcal emm types in an Indian community: the need to tailor multivalent vaccines. Clinical Infectious Diseases 2005; 40: 46-51. Duckworth D. Streptococcus pyogenes. http://medinfo.ufl.edu/year2/mmid/bms5300/bugs/strpyoge.html. 1999. Farlander. Streptococcus pyogenes – killer flesh-eating bacteria. http://www.bbc.co.uk/dna/h2g2/A907481. 2003. Ferretti JJ, McShan WM, Ajdic D, et al. Complete gemone sequence of an M1 strain of Streptococcus pyogenes. Proceedings of the National Academy of Sciences 2001; 98(8): 4658-4663. Geetha D. Glomerulonephritis, poststreptococcal. http://www.emedicine.com/med/topic889.htm. 2004. Haorui Pharma-Chem Inc. Vancomycin HCl. http://www.haoruiusa.com/API/Vancomycin.htm. 2005. Horváth A, Olive C, Karpati L, et al. Toward the development of a synthetic group A streptococcal vaccine of high purity and broad protective coverage. J. Med. Chem. 2004; 47(16): 4100-4104. Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: the immune system in health and disease. Sixth Ed. New York: Garland Science Publishing. 2005. Kessenich CR, Bahl A. Necrotizing fasciitis: understanding the deadly results of the uncommon ‘flesh-eating bacteria.’ AJN 2004; 104(9): 51-55. Kotloff KL, Dale JB. Progress in group A streptococcal vaccine development. The Pediatric Infectious Disease Journal 2004; 23(8): 765-766. McMillan DJ, Davies MR, Browning CL, Good MF, Sriprakash KS. Prospecting for new group A streptococcal vaccine candidates. Indian J Med Res 2004; 119(Suppl): 121-125. Meador RJ. Acute rheumatic fever. http://www.emedicine.com/med/topic2922.htm. 2004. Medina E, Chhatwal GS. The potential for vaccine development against rheumatic fever. Indian Heart Journal 2002; 54(1): 93-98. References

  32. Medina, E, Goldmann O, Toppel AW, Chhatwal GS. Survival of Streptococcus pyogenes within host phagocytic cells: a pathogenic mechanism for persistence and systemic invasion. JID 2003; 187: 597-603. Mitchell, TJ. The pathogenesis of streptococcal infections: from tooth decay to meningitis. Nature Reviews 2003; 1: 219-230. Molinari, G, Rohde M, Guzmán CA, Chhatwal GS. Two distinct pathways for the invasion of Streptococcus pyogenes in non-phagocytic cells. Cellular Microbiology 2000; 2(2): 145-154. Nakagawa I, Amano A, Mizushima N, et al. Autophagy defends cells against invading group A Streptococcus. Science 2004; 306: 1037-1040. National Institutes of Health. Vancomycin (systemic). http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202590.html. 1999. Olive C, Batzloff MR, Toth I. Lipid core peptide technology and group A streptococcal vaccine delivery. Expert Rev. Vaccines 2004; 3(1): 43-58. Pérez-Caballero D, García-Laorden I, Cortés G, et al. Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules. The Journal of Immunology 2004; 173: 6899-6904. Schleiss MR. Streptococcal infection, group A. http://www.emedicine.com/ped/topic2702.htm. 2005. Schwartz RA. Necrotizing fasciitis. http://www.emedicine.com/derm/topic743.htm. 2005. Sharma S. Streptococcus group A infections. http://www.emedicine.com/med/topic2184.htm. 2004. Stevens DL, Madaras-Kelly KJ, Richards DM. In vitro antimicrobial effects of various combinations of penicillin and clindamycin against four strains of Streptococcus pyogenes. Antimicrobial Agents and Chemotherapy 1998; 42(5): 1266-1268. Stulberg M, Smith CM, Scogin S, Sacks H. Streptococcus. http://biology.kenyon.edu/Microbial_Biorealm/bacteria/gram-positive/streptococcus/streptococcus.htm?name=Streptococcaceae. 2002. Todar, K. Streptococcus pyogenes. http://textbookofbacteriology.net/streptococcus.html. 2002. Wizemann TM, Adamou JE, Langermann S. Adhesins as targets for vaccine development. Emerging Infectious Diseases 1999; 5(3): 395-403. References Cont’d

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