Streptococcus pyogenes

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Streptococcus pyogenes
Streptococcus pyogenes.jpg
S. pyogenes bacteria at 900x magnification.
Scientific classification
Kingdom: Eubacteria
Phylum: Firmicutes
Class: Cocci
Order: Lactobacillales
Family: Streptococcaceae
Genus: Streptococcus
Species: S. pyogenes
Binomial name
Streptococcus pyogenes
Rosenbach 1884

Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections.[1] S. pyogenes displays streptococcal group A antigen on its cell wall. S. pyogenes typically produces large zones of beta-hemolysis (the complete disruption of erythrocytes and the release of hemoglobin) when cultured on blood agar plates, and are therefore also called Group A (beta-hemolytic) Streptococcus (abbreviated GABHS).

Streptococci are catalase-negative. Under ideal conditions, S. pyogenes has an incubation period of approximately 1–3 days.[2] It is an infrequent, but usually pathogenic, part of the skin flora.

It is estimated that there are more than 700 million infections worldwide each year and over 650,000 cases of severe, invasive infections that have a mortality rate of 25%.[3] Early recognition and treatment are critical; diagnostic failure can result in sepsis and death.[4][5]

Serotyping[edit]

In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its M protein, a virulence factor displayed on its surface.[6] Later in 1946, Lancefield described the serologic classification of S. pyogenes isolates based on their surface T antigen.[7] Four of the 20 T antigens have been revealed to be pili, which are used by bacteria to attach to host cells.[8] Over 220 M serotypes and approximately 20 T serotypes are known.

Pathogenesis[edit]

S. pyogenes is the cause of many important human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases.[1] Infections typically begin in the throat or skin. Examples of mild S. pyogenes infections include pharyngitis ("strep throat") and localized skin infection ("impetigo"). Erysipelas and cellulitis are characterized by multiplication and lateral spread of S. pyogenes in deep layers of the skin. S. pyogenes invasion and multiplication in the fascia can lead to necrotizing fasciitis, a life-threatening condition requiring surgery.

Infections due to certain strains of S. pyogenes can be associated with the release of bacterial toxins. Throat infections associated with release of certain toxins lead to scarlet fever. Other toxigenic S. pyogenes infections may lead to streptococcal toxic shock syndrome, which can be life-threatening.[1]

S. pyogenes can also cause disease in the form of postinfectious "nonpyogenic" (not associated with local bacterial multiplication and pus formation) syndromes. These autoimmune-mediated complications follow a small percentage of infections and include rheumatic fever and acute postinfectious glomerulonephritis. Both conditions appear several weeks following the initial streptococcal infection. Rheumatic fever is characterised by inflammation of the joints and/or heart following an episode of streptococcal pharyngitis. Acute glomerulonephritis, inflammation of the renal glomerulus, can follow streptococcal pharyngitis or skin infection.

This bacterium remains acutely sensitive to penicillin. Failure of treatment with penicillin is generally attributed to other local commensal organisms producing β-lactamase, or failure to achieve adequate tissue levels in the pharynx. Certain strains have developed resistance to macrolides, tetracyclines, and clindamycin.

Virulence factors[edit]

S. pyogenes has several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.[9] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils.[1] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells.[10] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen.[1] However, the M protein is also the weakest point in this pathogen's defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes. M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.


Name Description
Streptolysin O An exotoxin that is one of the bases of the organism's beta-hemolytic property.
Streptolysin S A cardiotoxic exotoxin that is another beta-hemolytic component. Streptolysin S is not immunogenic and O2 stable. A potent cell poison affecting many types of cell including neutrophils, platelets, and sub-cellular organelles, streptolysin S causes an immune response and detection of antibodies to it; antistreptolysin O (ASO) can be clinically used to confirm a recent infection.
Streptococcal pyrogenic exotoxin A (SpeA) Superantigens secreted by many strains of S. pyogenes. This pyrogenic exotoxin is responsible for the rash of scarlet fever and many of the symptoms of streptococcal toxic shock syndrome.
Streptococcal pyrogenic exotoxin C (SpeC)
Streptokinase Enzymatically activates plasminogen, a proteolytic enzyme, into plasmin, which in turn digests fibrin and other proteins.
Hyaluronidase It is widely assumed hyaluronidase facilitates the spread of the bacteria through tissues by breaking down hyaluronic acid, an important component of connective tissue. However, very few isolates of S. pyogenes are capable of secreting active hyaluronidase due to mutations in the gene that encode the enzyme. Moreover, the few isolates that are capable of secreting hyaluronidase do not appear to need it to spread through tissues or to cause skin lesions.[11] Thus, the true role of hyaluronidase in pathogenesis, if any, remains unknown.
Streptodornase Most strains of S. pyogenes secrete up to four different DNases, which are sometimes called streptodornase. The DNases protect the bacteria from being trapped in neutrophil extracellular traps (NETs) by digesting the NET's web of DNA, to which are bound neutrophil serine proteases that can kill the bacteria.[12]
C5a peptidase C5a peptidase cleaves a potent neutrophil chemotaxin called C5a, which is produced by the complement system.[13] C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.[14]
Streptococcal chemokine protease The affected tissue of patients with severe cases of necrotizing fasciitis are devoid of neutrophils.[15] The serine protease ScpC, which is released by S. pyogenes, is responsible for preventing the migration of neutrophils to the spreading infection.[16] ScpC degrades the chemokine IL-8, which would otherwise attract neutrophils to the site of infection. C5a peptidase, although required to degrade the neutrophil chemotaxin C5a in the early stages of infection, is not required for S. pyogenes to prevent the influx of neutrophils as the bacteria spread through the fascia.[14][16]

Diagnosis[edit]

Usually, a throat swab is taken to the laboratory for testing. A Gram stain is performed to show Gram-positive cocci in chains. Then, the organism is cultured on blood agar with an added bacitracin antibiotic disk to show beta-hemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Culture on non-blood containing agar then, perform catalase test, which should show a negative reaction for all Streptococci. S. pyogenes is CAMP (not to be confused with cAMP) and hippurate tests negative. Serological identification of the organism involves testing for the presence of group A specific polysaccharide in the bacterium's cell wall using the Phadebact test.[17][18]

Treatment[edit]

The treatment of choice is penicillin and the duration of treatment is well established as being 10 days minimum.[19] There has been no reported instance of penicillin resistance to date, although since 1985, there have been many reports of penicillin tolerance.[20]

Macrolides, chloramphenicol, and tetracyclines may be used if the strain isolated has been shown to be sensitive, but resistance is much more common.

Prevention[edit]

No vaccines are currently available to protect against S. pyogenes infection, although there has been research into the development of one. Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and people that will be needed for appropriate trials for safety and efficacy of the vaccine.[21]

Applying in bionanotechnology[edit]

Many S. pyogenes proteins have unique properties, which have been harnessed in recent years to produce a highly specific "superglue"[22][23] and a route to enhance the effectiveness of antibody therapy.[24]

See also[edit]

References[edit]

  1. ^ a b c d e Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9. 
  2. ^ http://www.dhs.wisconsin.gov/communicable/FactSheets/StreptococcalPharyngitis.htm  Missing or empty |title= (help)
  3. ^ Aziz RK, Kansal R, Aronow BJ, et al. (2010). "Microevolution of Group A Streptococci In Vivo: Capturing Regulatory Networks Engaged in Sociomicrobiology, Niche Adaptation, and Hypervirulence". In Ahmed, Niyaz. PLoS ONE 5 (4): e9798. doi:10.1371/journal.pone.0009798. PMC 2854683. PMID 20418946. Retrieved 2011-08-12. 
  4. ^ Jim Dwyer (July 11, 2012). "An Infection, Unnoticed, Turns Unstoppable". The New York Times. Retrieved July 12, 2012. 
  5. ^ Jim Dwyer (July 18, 2012). "After Boy’s Death, Hospital Alters Discharging Procedures". The New York Times. Retrieved July 19, 2012. 
  6. ^ Lancefield RC (1928). "The antigenic complex of Streptococcus hemolyticus". J Exp Med 47 (1): 9–10. doi:10.1084/jem.47.1.91. 
  7. ^ Lancefield RC, Dole VP (1946). "The properties of T antigen extracted from group A hemolytic streptococci". J Exp Med 84 (5): 449–71. doi:10.1084/jem.84.5.449. 
  8. ^ Mora M, Bensi G, Capo S, et al. (2005). "Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens". Proc Natl Acad Sci USA 102 (43): 15641–6. doi:10.1073/pnas.0507808102. PMC 1253647. PMID 16223875. 
  9. ^ Patterson MJ (1996). Streptococcus. In: Baron's Medical Microbiology (Baron S et al., eds.) (4th ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1. 
  10. ^ Bisno AL, Brito MO, Collins CM (2003). "Molecular basis of group A streptococcal virulence". Lancet Infect Dis 3 (4): 191–200. doi:10.1016/S1473-3099(03)00576-0. PMID 12679262. 
  11. ^ Starr C, Engleberg N (2006). "Role of Hyaluronidase in Subcutaneous Spread and Growth of Group A Streptococcus". Infect Immun 74 (1): 40–8. doi:10.1128/IAI.74.1.40-48.2006. PMC 1346594. PMID 16368955. 
  12. ^ Buchanan J, Simpson A, Aziz R, Liu G, Kristian S, Kotb M, Feramisco J, Nizet V (2006). "DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps". Curr Biol 16 (4): 396–400. doi:10.1016/j.cub.2005.12.039. PMID 16488874. 
  13. ^ Wexler D, Chenoweth D, Cleary P (1985). "Mechanism of action of the group A streptococcal C5a inactivator". Proc Natl Acad Sci USA 82 (23): 8144–8. doi:10.1073/pnas.82.23.8144. PMC 391459. PMID 3906656. 
  14. ^ a b Ji Y, McLandsborough L, Kondagunta A, Cleary P (1996). "C5a peptidase alters clearance and trafficking of group A streptococci by infected mice". Infect Immun 64 (2): 503–10. PMC 173793. PMID 8550199. 
  15. ^ Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn L, Nizet V, Ravins M, Jaffe J, Peyser A, Moses A, Hanski E (2004). "Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections". Lancet 363 (9410): 696–703. doi:10.1016/S0140-6736(04)15643-2. PMID 15001327. 
  16. ^ a b Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E (2006). "A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues". EMBO J 25 (19): 4628–37. doi:10.1038/sj.emboj.7601327. PMC 1589981. PMID 16977314. 
  17. ^ Kellogg JA, Bankert DA, Elder CJ, Gibbs JL, Smith MC (September 2001). "Identification of Streptococcus pneumoniae revisited". J. Clin. Microbiol. 39 (9): 3373–5. doi:10.1128/jcm.39.9.3373-3375.2001. PMC 88350. PMID 11526182. 
  18. ^ Burdash NM, West ME (March 1982). "Identification of Streptococcus pneumoniae by the Phadebact coagglutination test". J. Clin. Microbiol. 15 (3): 391–4. PMC 272105. PMID 7076811. 
  19. ^ Falagas ME, Vouloumanou EK, Matthaiou DK, Kapaskelis AM, Karageorgopoulos DE (2008). "Effectiveness and safety of short-course vs long-course antibiotic therapy for group a beta hemolytic streptococcal tonsillopharyngitis: a meta-analysis of randomized trials". Mayo Clin Proc 83 (8): 880–9. doi:10.4065/83.8.880. PMID 18674472. 
  20. ^ Kim KS, Kaplan EL (1985). "Association of penicillin tolerance with failure to eradicate group A streptococci from patients with pharyngitis". J Pediatr 107 (5): 681–4. doi:10.1016/S0022-3476(85)80392-9. PMID 3903089. 
  21. ^ "Initiative for Vaccine Research (IVR) - Group A Streptococcus". World Health Organization. Retrieved 15 June 2012. 
  22. ^ http://www.ox.ac.uk/media/science_blog/120221.html
  23. ^ Zakeri, B. (2012). "Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin". Proceedings of the National Academy of Sciences 109 (12): E690–7. doi:10.1073/pnas.1115485109. PMC 3311370. PMID 22366317. 
  24. ^ Baruah, K. (2012). "Selective Deactivation of Serum IgG: A General Strategy for the Enhancement of Monoclonal Antibody Receptor Interactions". Journal of Molecular Biology 420 (1-2): 1–7. doi:10.1016/j.jmb.2012.04.002. PMID 22484364. 

Further reading[edit]