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Panton-Valentine leukocidin



  Panton-Valentine leukocidin (PVL) is a cytotoxin—one of the β-pore forming toxins. The presence of PVL is associated with increased virulence of certain strains (isolates) of Staphylococcus aureus. It is present in the majority [1] of CA-MRSA isolates studied[2] [3] and is the cause of necrotic lesions involving the skin or mucosa, including necrotic hemorrhagic pneumonia. PVL is produced from the genetic material of a bacteriophage which infects Staphylococcus aureus, making it more virulent.[4]

Additional recommended knowledge

Contents

History

It was initially discovered by Van deVelde in 1894 due to its ability to lyse leukocytes. It was named after Panton and Valentine when they associated it with soft tissue infections in 1932. [5] [6]

Mechanism of action

Exotoxins such as PVL constitute essential components of the virulence mechanisms of s. aureus. Nearly all strains secrete lethal factors which convert host tissues into nutrients required for bacterial growth.[7]

PVL is a member of the synergohymenotropic toxin family that induces pores in the membranes of cells.[8] The PVL factor is encoded in a prophage—designated as Φ-PVL—which is a virus integrated into the s. aureus bacterial chromosome. Its genes secrete two proteins—toxins designated LukS-PV and LukF-PV, 33 and 34 kDa in size. These act together as subunits, assembling in the membrane of host defense cells, particularly white blood cells, monocytes and macrophages.[9] The subunits fit together and form a ring with a central pore through which cell contents leak and which acts as a superantigen.[10][8]

Clinical effects

PVL causes leukocyte destruction and necrotizing ("flesh-eating") pneumonia, an aggressive condition that often kills patients within 72 hours.[11] Comparing cases of staphylococcal necrotizing pneumonia, 85% of community-acquired (CAP) cases wer PVL positive, while none of the hospital-acquired cases were. CAP afflicted younger and healthier patients, and yet had a worse outcome (>40% mortality.) [8] It has played a role in a number of outbreaks of fatal bacterial infections.[12] PVL may increase the expression of staphylococcal protein A, a key pro-inflammatory factor for pneumonia.[13]

Epidemiology

Panton-Valentine leukocidin (PVL) is one of many toxins associated with S. aureus infection. Because it can be found in virtually all CA-MRSA strains that cause soft-tissue infections, it was long described as a key virulence factor, allowing the bacteria to target and kill specific white blood cells known as neutrophils. This view was challenged, however, when it was shown that removal of PVL from the two major epidemic CA-MRSA strains resulted in no loss of infectivity or destruction of neutrophils in a mouse model.[14] [15]

Genetic analysis shows that PVL CA-MRSA has emerged several times, on different continents, rather than being the worldwide spread of a single clone.[16]

References

  1. ^ Centers for Disease Control and Prevention (CDC) (2007-20-24). CA-MRSA Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA). Retrieved on 2007-11-01.
  2. ^ Szmiegielski S, Prevost G, Monteil H, et al. (1999;). "Leukocidal toxins of staphylococci.". Zentralbl Bakteriol 289:: 185–201..
  3. ^ Kaneko J, Kamio Y. (2004;). "Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes.". Biosci Biotechnol Biochem 68:: 981–1003..
  4. ^ Lina G, Piémont Y, Godail-Gamot F, Bes M, Peter M, Gauduchon V, Vandenesch F, Etienne J (1999). "Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia.". Clin Infect Dis 29 (5): 1128-32. PMID 10524952. Retrieved on 2006-09-01.
  5. ^ Panton, P.N., Came, M.B., Valentine, F.C.O., Lond, M.R.C.P. (1932-03). "Staphylococcal Toxin" (pdf). The Lancet 1: 506-508. Retrieved on 2007-12-06.
  6. ^ Boyle-Vavra S, Daum RS (2007). "Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton–Valentine leukocidin". Lab Invest 87: 3–9. doi:10.1038/labinvest.3700501. PMID 17146447.
  7. ^ Karim Boubaker. "CDC - Panton-Valentine Leukocidin and Staphyloccoccal Skin Infections in Schoolchildren". Emerging Infectious Diseases. Retrieved on 2007-12-08.
  8. ^ a b c Suzanne F. Bradley (2006-02-22). The Role of Toxins in the Changing Epidemiology and Clinical Presentation of Staphylococcal Pneumonia. Retrieved on 2007-12-08.
  9. ^ Melles DC, van Leeuwen WB, Boelens HAM, Peeters JK, Verbrugh HA, van Belkum A. (2006 Jul). "Panton-Valentine leukocidin genes in Staphylococcus aureus" (letter). Emerg Infect Dis Serial on web. Retrieved on 2007-12-07.
  10. ^ Derisinski, Stan (2005 Jan 24). "Methicillin-Resistant Staphylococcus aureus: An Evolutionary, Epidemiologic, and Therapeutic Odyssey.". Clin Infect Dis 40(4):562-73. Retrieved on 2007-12-07.
  11. ^ "Staph Toxin Can Trigger Deadly Pneumonia", Forbes, 2007-10-18. Retrieved on 2007-10-18. 
  12. ^ Nigel Hawkes. Baby's death linked to hospital bug. Retrieved on December 22, 2006.
  13. ^ "Staphylococcus aureus Toxin Can Cause Necrotizing Pneumonia", Medscape, 2007-01-18. Retrieved on 2007-01-18. 
  14. ^ MRSA Toxin Acquitted: Study Clears Suspected Key to Severe Bacterial Illness, NIH news release, Nov. 6, 2006
  15. ^ Voyich JM, Otto M, Mathema B, et al (2006). "Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?". J. Infect. Dis. 194 (12): 1761–70. doi:10.1086/509506. PMID 17109350. Retrieved on 2007-12-06.
  16. ^ Vandenesch F, Naimi T, Enright M, Lina G, Nimmo G, Heffernan H, Liassine N, Bes M, Greenland T, Reverdy M, Etienne J (August 2003). "Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence". Emerg Infect Dis 9 (8): 978-84. PMID 12967497. Retrieved on 2007-02-15.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Panton-Valentine_leukocidin". A list of authors is available in Wikipedia.
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