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 majoritycite web
title= Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA)
url=http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html CA-MRSA
accessdate=2007-11-01
author=Centers for Disease Control and Prevention (CDC)
date=2007-20-24] of community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates studiedcite journal
url=http://md1.csa.com/partners/viewrecord.php?requester=gs&collection=ENV&recid=4585549&q=&uid=791585049&setcookie=yes
author=Szmiegielski S, Prevost G, Monteil H, et al.| title=Leukocidal toxins of staphylococci. | journal=Zentralbl Bakteriol | date=1999;
volume=289: | pages=185–201.] cite journal | author=Kaneko J, Kamio Y.
title=Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes.
journal=Biosci Biotechnol Biochem | date=2004; | volume=68: | pages=981–1003.
doi=10.1271/bbb.68.981] and is the cause of necrotic ("flesh-eating") lesions involving the skin or mucosa, including necrotic hemorrhagic pneumonia. PVL creates pores in the membranes of infected cells. PVL is produced from the genetic material of a bacteriophage which infects "Staphylococcus aureus", making it more virulent.cite journal
author = Lina G, Piémont Y, Godail-Gamot F, Bes M, Peter M, Gauduchon V, Vandenesch F, Etienne J
title = Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia.
journal = Clin Infect Dis | volume = 29 | issue = 5 | pages = 1128–32 | year = 1999 | pmid = 10524952
accessdate=2006-09-01
doi = 10.1086/313461]

History

It was initially discovered by Van deVelde in 1894 due to its ability to lyse leukocytes. It was named after Sir Philip Noel Panton and Francis Valentine when they associated it with soft tissue infections in 1932.cite journal|journal = The Lancet
url=https://dspace.ubib.eur.nl/bitstream/1765/7927/1/PVL.pdf
format = pdf
title=Staphylococcal Toxin|author=Panton, P.N., Came, M.B., Valentine, F.C.O., Lond, M.R.C.P.
volume= 1 | year= 1932-03| pages= 506–508|accessdate=2007-12-06] cite journal | author= Boyle-Vavra S, Daum RS | title=Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton–Valentine leukocidin | journal=Lab Invest | date=2007 | volume=87 | pages=3–9 | doi=10.1038/labinvest.3700501 | pmid=17146447 ]

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.cite journal |journal=Emerging Infectious Diseases
author=Karim Boubaker|url=http://www.cdc.gov/ncidod/EID/vol10no1/03-0144.htm |title=CDC - Panton-Valentine Leukocidin and Staphyloccoccal Skin Infections in Schoolchildren |accessdate=2007-12-08 |format= |work=]

PVL is a member of the synergohymenotropic toxin family that induces pores in the membranes of cells.cite web |url=http://www.medscape.com/viewarticle/521338_6 |title=The Role of Toxins in the Changing Epidemiology and Clinical Presentation of Staphylococcal Pneumonia
date=2006-02-22|author=Suzanne F. Bradley
accessdate=2007-12-08 | page=6|work=] 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.cite journal
author=Melles DC, van Leeuwen WB, Boelens HAM, Peeters JK, Verbrugh HA, van Belkum A.
title= Panton-Valentine leukocidin genes in Staphylococcus aureus |format = letter
journal =Emerg Infect Dis |year= 2006 Jul| volume=Serial on web
url =http://www.cdc.gov/ncidod/EID/vol12no07/05-0865.htm
accessdate=2007-12-07] The subunits fit together and form a ring with a central pore through which cell contents leak and which acts as a superantigen.cite journal
author=Derisinski, Stan
title= Methicillin-Resistant Staphylococcus aureus: An Evolutionary, Epidemiologic, and Therapeutic Odyssey.
url=http://www.journals.uchicago.edu/CID/journal/issues/v40n4/34808/34808.web.pdf
journal= Clin Infect Dis|year= 2005 Feb 15|volume=40(4):562-73|date=2005 Jan 24|accessdate=2007-12-07
format= Dead link|date=May 2008 – ^{[http://scholar.google.co.uk/scholar?hl=en&lr=&q=author%3A+intitle%3AMethicillin-Resistant+Staphylococcus+aureus%3A+An+Evolutionary%2C+Epidemiologic%2C+and+Therapeutic+Odyssey.&as_publication=Clin+Infect+Dis&as_ylo=2005 Feb 15&as_yhi=2005 Feb 15&btnG=Search Scholar search]} ]

Clinical effects

PVL causes leukocyte destruction and necrotizing ("flesh-eating") pneumonia, an aggressive condition that often kills patients within 72 hours. [cite news
url=http://www.forbes.com/forbeslife/health/feeds/hscout/2007/01/18/hscout601101.html
title=Staph Toxin Can Trigger Deadly Pneumonia |date= 2007-10-18 | publisher=Forbes
accessdate=2007-10-18] Comparing cases of staphylococcal necrotizing pneumonia, 85% of community-acquired (CAP) cases were PVL positive, while none of the hospital-acquired cases were. CAP afflicted younger and healthier patients, and yet had a worse outcome (>40% mortality.) It has played a role in a number of outbreaks of fatal bacterial infections.cite web
title= Baby's death linked to hospital bug |author = Nigel Hawkes
url = http://www.timesonline.co.uk/article/0,,2-2516306,00.html
accessdate= December 22 | accessyear=2006] PVL may increase the expression of staphylococcal protein A, a key pro-inflammatory factor for pneumonia. [cite news
url= http://www.medscape.com/viewarticle/550968 | publisher=Medscape
date= 2007-01-18 | accessdate=2007-01-18
title=Staphylococcus aureus Toxin Can Cause Necrotizing Pneumonia]

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. [ [http://www3.niaid.nih.gov/news/newsreleases/2006/staphtoxin.htm MRSA Toxin Acquitted: Study Clears Suspected Key to Severe Bacterial Illness] , NIH news release, Nov. 6, 2006] cite journal
author=Voyich JM, Otto M, Mathema B, "et al"
title=Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?
journal=J. Infect. Dis. |volume=194 |issue=12 |pages=1761–70 |year=2006 |pmid=17109350
doi=10.1086/509506 |url=http://www.journals.uchicago.edu/cgi-bin/resolve?JID36574
accessdate=2007-12-06]

Genetic analysis shows that PVL CA-MRSA has emerged several times, on different continents, rather than being the worldwide spread of a single clone.cite journal
author=Vandenesch F, Naimi T, Enright M, Lina G, Nimmo G, Heffernan H, Liassine N, Bes M, Greenland T, Reverdy M, Etienne J
title= Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence
journal=Emerg Infect Dis |volume=9 |issue=8 |pages=978–84 |year=2003
month=August |accessdate=2007-02-15 |pmid=12967497
url= http://www.cdc.gov/ncidod/Eid/vol9no8/pdfs/03-0089.pdf ]

References

External links

*