Panton-valentine leukocidin facilitates the escape of staphylococcus aureus from human keratinocyte endosomes and induces apoptosis

Chia Yu Chi, Chia Chun Lin, I. Chuang Liao, Yi Chuan Yao, Fan Ching Shen, Ching Chuan Liu, Chiou Feng Lin

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)224-235
Number of pages12
JournalJournal of Infectious Diseases
Volume209
Issue number2
DOIs
Publication statusPublished - Jan 15 2014
Externally publishedYes

Keywords

  • Endosome
  • Keratinocyte
  • Panton-Valentine leukocidin
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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