PVL

PVL stands for a cytotoxin Panton Valentine Leukocidin, found as a virulence factor in methicillin resistant Staphylococcus aureus (MRSA). It was named after Sir Philip Noel Panton and Francis Valentine [1]. The cytotoxin is encoded by two genes viz. lukS-PV and lukF-PV [2]. The resistance of MRSA to β-lactam antibiotics is associated with penicillin-binding protein 2a. This is encoded by the mecA gene.
The PVL was associated with soft tissue infection as described by the discoverers in 1932 [1,3]. It is a member of synergohymenotropic toxin family inducing pores in the membranes of cells. PVL producing MRSA usually cause mild skin or soft tissue infections. Nevertheless, severe cases of necrotizing pneumonia and sepsis have also been reported [4]. The first PVL positive MRSA was observed in the late 1990. These strains have become globally distributed now [5]. It has reported to increase the pathogenicity of S. aureus by necrosis, accelerating apoptosis and destruction of polymorphonuclear and mononuclear cells [6].PVL is commonly used as a marker for community acquired MRSA, responsible for soft-tissue and deep dermal infections [7,8]. The risk of acquiring the infection is increased with close contact, contaminated items, crowding, cleanliness and cuts and grazes.

PVL stands for Panton-Valentine leukocidin, which is a toxin produced by certain strains of Staphylococcus aureus bacteria. It is a pore-forming toxin that targets and damages white blood cells (leukocytes), particularly neutrophils. PVL is encoded by the lukS-PV and lukF-PV genes, which are part of a bacteriophage integrated into the bacterial genome.

Mechanism of Action:

1. Binding to Host Cells: PVL binds to specific receptors on the surface of white blood cells, particularly neutrophils.
2. Formation of Pores: Once bound, PVL oligomerizes and forms pores in the cell membrane of the white blood cell.
3. Disruption of Cell Function: The pores disrupt the integrity of the cell membrane, leading to ion leakage and cell death through necrosis or apoptosis.
4. Impairment of Host Defense: By targeting and damaging white blood cells, PVL impairs the host's immune response, making it easier for Staphylococcus aureus to evade immune clearance and establish infection.

Clinical Significance:

• Skin and Soft Tissue Infections: PVL-positive Staphylococcus aureus strains are commonly associated with skin and soft tissue infections, including furuncles (boils), abscesses, cellulitis, and necrotizing fasciitis.
• Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA): PVL-positive strains are often implicated in cases of CA-MRSA, which can cause severe and sometimes fatal infections, especially in otherwise healthy individuals.
• Pneumonia: PVL has also been associated with necrotizing pneumonia, a severe form of lung infection characterized by tissue destruction and abscess formation.
• Increased Virulence: PVL is considered a virulence factor that contributes to the pathogenicity of Staphylococcus aureus strains, particularly in the context of skin and soft tissue infections and necrotizing pneumonia.

Detection:

• PVL can be detected using molecular methods such as polymerase chain reaction (PCR) to amplify and identify the lukS-PV and lukF-PV genes.
• Phenotypic assays, such as culture-based assays or leukocyte lysis assays, can also be used to detect PVL activity.

Treatment Implications:

• The presence of PVL may influence treatment decisions, as PVL-positive strains have been associated with more severe infections and treatment failures.
• Infections caused by PVL-positive Staphylococcus aureus strains may require more aggressive antibiotic therapy and may be less responsive to certain antibiotics.

In summary, Panton-Valentine leukocidin (PVL) is a pore-forming toxin produced by some strains of Staphylococcus aureus, contributing to the virulence and severity of infections caused by these bacteria, particularly in the context of skin and soft tissue infections and necrotizing pneumonia.

References:

1.     Prevost G, Cribier B, Couppie P, Petiau P, Supersac G, Finck-Barbancon V,et al. Panton-Valentine leukocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by district genetic loci and have different biological activities. Infect Immun. 1995; 63:4121–9.

2.     Panton P, Valentine F. Staphylococcal toxin. Lancet. 1932;219(5662):506–8.

3.     Genestier AL, Michalete MC, Prévoset G, Bellot G, Chalabreysse L, Peyrol S, et al. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J Clin Invest. 2005; 115:3117–27.

4.     Maltezou HC, Giamarellou H. Community acquired methicillin resistant Staphylococcus aureus infections. Int J Antimicrob Agents. 2006;27:87–96.

5.     Gravet A, Rondeau M, Harf-Monteil C, Grunenberger F, Monteil F, Scheftel JM, et al. Predominant Staphylococcus aureus isolated from antibiotic-associated diarrhea is clinically relevant and produces enterotoxin A and the bicomponent toxin LukE-LukD. J Clin Microbiol. 1999;37:4012–9.

6.     Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, et al. Involvement of Panton- Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis. 1999;29: 1128–32.
7.     Havaei SA, Moghadam SO, Pourmand MR, Faghri J. Prevalence of genes encoding bi-component leukocidins among clinical isolates of methicillin-resistant Staphylococcus aureus. Iranian J Publ Health. 2010;39:8–14.
8.     Miller LG, Perdreau-Remington F, Rieg G, Mehdi H, Perlroth J, Bayer AS, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005; 352:1445–53.