Streptococcus pyogenes

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

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