Phenol-Soluble Modulin Peptides Contribute to Influenza A Virus-Associated Staphylococcus aureus Pneumonia
Dominik Alexander Bloes1, Emanuel Haasbach2, Carmen Hartmayer2
1Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, Tübingen, Germany.
Abstract:
Influenza A virus (IAV) infection is 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 strains are known to produce extraordinarily large amounts of phenol-soluble modulin (PSM) peptides, which are important cytotoxins and proinflammatory molecules that contribute 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 the secretion of the proinflammatory cytokine interleukin-8 (IL-8) in these cells. Both effects were boosted by previous infection with the 2009 swine flu pandemic IAV H1N1 strain, suggesting that PSMs may contribute to lung inflammation and damage in IAV-associated S. aureus pneumonia. Notably, the PSM-producing USA300 strain caused a higher mortality rate than did an isogenic PSM-deficient mutant in a mouse IAV-S. aureus pneumonia coinfection model, indicating that PSMs are major virulence factors in IAV-associated S. aureus pneumonia and may represent important targets for future anti-infective therapies.
Insights
Phenol-soluble modulin (PSM) peptides from Staphylococcus aureus worsen lung damage during influenza A virus (IAV) coinfection. PSMs are key virulence factors in IAV-associated pneumonia, suggesting new therapeutic targets.
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Influenza A virus (IAV) infections frequently lead to secondary bacterial pneumonia, a major cause of severe and fatal outcomes.
- Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly USA300 strains, are linked to severe, difficult-to-treat pneumonia following IAV infection.
- CA-MRSA produces high levels of phenol-soluble modulin (PSM) peptides, known cytotoxins and pro-inflammatory molecules, but their role in pneumonia was unclear.
Purpose of the Study:
- To investigate the impact of PSM peptides on human lung epithelial cells during IAV coinfection.
- To determine the role of PSMs as virulence factors in a mouse model of IAV-S. aureus pneumonia.
Main Methods:
- Assessed the cytotoxicity and interleukin-8 (IL-8) secretion induced by PSMs in human lung epithelial cells.
- Utilized a mouse model of IAV-S. aureus coinfection to compare the virulence of PSM-producing USA300 strain versus a PSM-deficient mutant.
Main Results:
- PSMs were found to be cytotoxic to human lung epithelial cells and induced IL-8 secretion.
- These effects were exacerbated by prior infection with the 2009 H1N1 IAV strain.
- The PSM-producing USA300 strain resulted in significantly higher mortality rates compared to the PSM-deficient mutant in the coinfection model.
Conclusions:
- PSMs contribute to lung inflammation and damage in IAV-associated S. aureus pneumonia.
- PSMs are significant virulence factors in this condition.
- PSMs represent potential targets for novel anti-infective therapies against severe pneumonia.
More Related Videos
10:47Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice
Published on: April 14, 2011
11:32Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
Related Concept Videos
02:28Leaky Scanning
01:28Gene Regulation in Microbial Communities: Quorum Sensing
01:29Pneumonia II: Pathophysiology
01:23Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...