title: Panton-Valentine leukocidin facilitates the escape of Staphylococcus aureus from human keratinocyte endosomes and induces apoptosis.
abstract: Skin and soft-tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as major health problems throughout the world. Most SSTI CA-MRSA strains produce Panton-Valentine leukocidin (PVL), but its contribution to CA-MRSA pathogenesis is poorly defined. Here, we used an endemic PVL-positive SSTI-causing CA-MRSA strain from Taiwan, together with an isogenic PVL-knockout mutant (Δpvl) and complemented PVL-positive derivative, to evaluate the role of PVL in the pathogenesis of CA-MRSA in the RHEK-1 human keratinocyte cell line and a rabbit skin infection model. We found that both PVL-positive CA-MRSA and isogenic Δpvl strains attached and were engulfed into endosomes of RHEK-1 cells within 1 hour following infection. However, by 2 hours after infection PVL-positive CA-MRSA more effectively disrupted endosomes, escaped into the cytoplasm, and replicated intracellularly. By 6 hours after infection, the PVL-positive strain caused significantly more caspase-dependent keratinocyte apoptosis than the isogenic Δpvl mutant. In the rabbit infection model, 1 week following infection the wild-type strain produced significantly more widespread lesions and cell apoptosis than the isogenic Δpvl mutant. These findings indicate that PVL is an important virulence factor that enables CA-MRSA to produce necrotizing skin infections by allowing the bacteria to escape from endosomes, replicate intracellularly, and induce apoptosis.
authors: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University.
authors: Chia-Yu
authors: CY
authors: Chi
authors: Chia-Chun
authors: CC
authors: Lin
authors: I-Chuang
authors: IC
authors: Liao
authors: Yi-Chuan
authors: YC
authors: Yao
authors: Fan-Ching
authors: FC
authors: Shen
authors: Ching-Chuan
authors: CC
authors: Liu
authors: Chiou-Feng
authors: CF
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001419:Bacteria; D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D017714:Community-Acquired Infections / Q000382:microbiology; D004195:Disease Models, Animal; D011992:Endosomes / Q000382:microbiology*; D005098:Exotoxins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology*; D007793:Lagomorpha; D007956:Leukocidins / Q000378:metabolism*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity*; D011817:Rabbits; D013207:Staphylococcal Skin Infections / Q000382:microbiology; D013624:Taiwan; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors
keywords: Panton-Valentine leukocidin; Staphylococcus aureus; endosome; keratinocyte