Panton-Valentine leukocidin (PVL) is a cytotoxin

Cytotoxicity

Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...

—one of the β-pore-forming toxins. The presence of PVL is associated with increased virulence

Virulence

Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 of certain strains (isolates) of Staphylococcus aureus

Staphylococcus aureus

Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

. It is present in the majority

of community-associated Methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...

 (CA-MRSA) isolates studied
and is the cause of necrotic lesion

Lesion

A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...

s involving the skin or mucosa, including necrotic hemorrhagic pneumonia

Pneumonia

Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

.
PVL creates pores in the membranes of infected cells. PVL is produced from the genetic material of a bacteriophage

Bacteriophage

A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

 that infects Staphylococcus aureus

Staphylococcus aureus

Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

, making it
more virulent.

History

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

Lysis

Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....

 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

Exotoxin

An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. 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...

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

Prophage

A prophage is a phage genome inserted and integrated into the circular bacterial DNA chromosome. A prophage, also known as a temperate phage, is any virus in the lysogenic cycle; it is integrated into the host chromosome or exists as an extrachromosomal plasmid. Technically, a virus may be called...

—designated as Φ-PVL—which is a virus integrated into the S. aureus bacterial chromosome

Nucleoid

The nucleoid is an irregularly-shaped region within the cell of a prokaryote that contains all or most of the genetic material. In contrast to the nucleus of a eukaryotic cell, it is not surrounded by a nuclear membrane. The genome of prokaryotic organisms generally is a circular, double-stranded...

.
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

Protein Data Bank

The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....

 as ID codes 1t5r and 1pvl respectively. See the PDBe article for more information on these structures.

LukS-PV and LukF-PV act together as subunits, assembling in the membrane of host defense cells, in particular, white blood cells, monocytes, 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

Superantigen

Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release...

.

Clinical effects

PVL causes leukocyte

White blood cell

White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

 destruction and necrotizing pneumonia, an aggressive condition that often kills patients within 72 hours.
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

Protein A

Protein A is a 40-60 kDa MSCRAMM surface protein originally found in the cell wall of the bacterium Staphylococcus aureus. It is encoded by the spa gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in...

, 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

Methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...

  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.

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