5 years ago

Phenol-soluble modulin peptides contribute to influenza-associated Staphylococcus aureus pneumonia.

Hartmayer C, Kretschmer D, Planz O, Klingel K, Peschel A, Hertlein T, Haasbach E, Bloes DA
Influenza A virus (IAV) infections are often followed by secondary bacterial lung infection, which is a major reason for severe, often fatal pneumonia. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA are known to produce extraordinarily high amounts of phenol-soluble modulin (PSM) peptides, important cytotoxins and proinflammatory molecules contributing to several types of S. aureus infection. However, their potential role in pneumonia has remained elusive. We determined the impact of PSMs on human lung epithelial cells and found that PSMs are cytotoxic and induce secretion of the proinflammatory cytokine IL-8 in these cells. Both effects were boosted by prior infection with 2009's swine flu pandemic IAV strain H1N1 suggesting that PSMs may contribute to lung inflammation and damage in IAV-associated S. aureus pneumonia. Notably, PSM-producing USA300 caused higher mortality than an isogenic PSM-deficient mutant in a mouse IAV/S. aureus pneumonia co-infection model indicating that PSMs are major virulence factors in IAV-associated S. aureus pneumonia and may represent important targets for future anti-infective therapies.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28893917

DOI: PubMed:28893917

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