Staphylococcus aureus Panton-Valentine Leukocidin Causes Necrotizing Pneumonia

Abstract

The Staphylococcus aureus Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by strains epidemiologically associated with the current outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and with the often-lethal necrotizing pneumonia. To investigate the role of PVL in pulmonary disease, we tested the pathogenicity of clinical isolates, isogenic PVL-negative and PVL-positive S. aureus strains, as well as purified PVL, in a mouse acute pneumonia model. Here we show that PVL is sufficient to cause pneumonia and that the expression of this leukotoxin induces global changes in transcriptional levels of genes encoding secreted and cell wall-anchored staphylococcal proteins, including the lung inflammatory factor staphylococcal protein A (Spa).

Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance

“…Broadspectrum immunosuppression with systemic cyclophosphamide and impairment of mucociliary clearance with intranasal formalin also allow for development of S. aureus pneumonia, independent of bacterial toxin production (9). Injection of PVL positive MRSA causes a rapidly fatal (20% survive 24 hours) necrotizing pneumonia in immunocompetent mice via transcription of genes coding for secreted and cell wall-anchored proteins including lung inflammatory factor staphylococcal protein A (10). Additionally, intranasal inoculation of 4-8 × 10 8 (but not 8 × 10 7 ) CFU of S. aureus Newman, a human clinical isolate, causes a rapidly fatal model of pneumonia in immunocompetent C57Bl/6 mice with evidence of bacterial growth in vivo associated with production of sortase A (11).…”

Clinical and economic outcomes in patients with community‐acquired Staphylococcus aureus pneumonia

“…This also extends the finding of previous case studies reporting that MRSA CAP with PVL toxin is associated with worse outcomes. [24][25][26][27][28][29][30] Moreover, we clearly document that PVL-positive strains are emerging as a cause of pulmonary infection in broader clinical scenarios. As such, physicians must remain vigilant for this toxin-producing strain.…”

“…23 Recent studies of acute pneumonia with animal models and in humans have suggested that the PVL toxin-alone or in combination with other virulence factors-is associated with the development of necrotizing pneumonia. [24][25][26][27][28][29][30] In our study, 23 patients with MRSA CAP had strains that contained PVL toxin, and these patients had longer stays in hospital and higher total hospital charges than those with MRSA CAP not containing the PVL toxin. This is an important finding, as length of stay is an important proxy for morbidity and case severity.…”

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

“…In vitro experiments have demonstrated that the activation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway in infected pulmonary epithelial cells results in inflammation enhancement via IL-8 expression; furthermore, intracellular S. aureus can lead, after an initial lag period, to the apoptosis of these cells. [21,22] In necrotizing pneumonia, the key virulence factors of S. aureus associated with the apoptosis of lung cells were shown to be pore-forming toxins, namely Panton-Valentine leukocidin (PVL) and alpha-hemolysin [23,24]. …”