Panton-Valentine leukocidin facilitates the escape of Staphylococcus aureus from human keratinocyte endosomes and induces apoptosis.
J Infect Dis
; 209(2): 224-35, 2014 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-23956440
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Toxinas Bacterianas
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Queratinócitos
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Apoptose
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Fatores de Virulência
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Exotoxinas
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Staphylococcus aureus Resistente à Meticilina
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Leucocidinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article