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 ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

''. It is present in the majority of community-associated methicillin-resistant ''Staphylococcus aureus'' (CA-MRSA) isolates studied and is the cause of necrotic lesions involving the skin or

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

, including necrotic hemorrhagic pneumonia. PVL creates pores in the membranes of infected cells. PVL is produced from the genetic material of a

bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...

that infects ''

'', making it more virulent.

History

It was initially discovered by Van deVelde in 1894 due to its ability to

lyse Lyse may refer to: * Lyse Abbey, a former Cistercian abbey in Norway * Lyse, an alternative name of Lysebotn, Norway * Lyse Energi, a Norwegian power company * Łyse, Masovian Voivodeship, a village in east-central Poland * Łyse, Podlaskie Voivode ...

leukocytes. It was named after Sir Philip Noel Panton and Francis Valentine when they associated it with soft tissue infections in 1932.

Mechanism of action

Exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, simi ...

s such as PVL constitute essential components of the virulence mechanisms of ''S. aureus''. Nearly all strains secrete lethal factors that convert host tissues into nutrients required for bacterial growth. PVL is a member of the synergohymenotropic toxin family that induces pores in the membranes of cells. The PVL factor is encoded in a

prophage A prophage is a bacteriophage (often shortened to "phage") genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is the c ...

—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. The structures of both proteins have been solved in the soluble forms, and are present in the PDB as ID codes and respectively. LukS-PV and LukF-PV act together as subunits, assembling in the membrane of host defense cells, in particular, white blood cells,

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...

, and macrophages. The subunits fit together and form a ring with a central pore through which cell contents leak and which acts as a

superantigen Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are p ...

. Other authors contribute the differential response of MRSA subtypes to phenol-soluble modulin (PSM) peptides and not to PVL.

Clinical effects

PVL causes

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

destruction and necrotizing pneumonia, an aggressive condition that can kill up to 75% of patients. 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. PVL may increase the expression of staphylococcal protein A, a key pro-inflammatory factor for 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.MRSA Toxin Acquitted: Study Clears Suspected Key to Severe Bacterial Illness
, NIH news release, Nov. 6, 2006 Genetic analysis shows that PVL CA-MRSA has emerged several times, on different continents, rather than being the worldwide spread of a single clone.

References

External links

* {{DEFAULTSORT:Panton-Valentine Leukocidin Bacterial toxins Staphylococcaceae Virulence factors