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Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of
Jessica Baude1, Sylvère Bastien1, Yves Gillet1,2
1Centre International de Recherche en Infectiologie, Université de Lyon; Inserm U1111; Ecole Normale Supérieure de Lyon; Université Lyon 1, CNRS, UMR5308; Lyon, France.
Background:
Necrotizing soft tissue infections (NSTIs) caused by group A Streptococcus (GAS) and occasionally by Staphylococcus aureus (SA) frequently involve the deep fascia and often lead to muscle necrosis.
Methods:
To assess the pathogenicity of GAS and S. aureus for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed in these cells. Bloodstream infections (BSI-SA) and noninvasive coagulase-negative staphylococci (CNS) isolates were used as controls.
Results:
NSTI-SA and BSI-SA exhibited stronger internalization into human keratinocytes and myoblasts than NSTI-GAS or CNS. S. aureus internalization reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%). Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA was attributed to higher levels of psmα and RNAIII transcripts in NSTI-SA. However, the 2 groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants.
Conclusions:
Our findings suggest a factor in NSTI-SA severity is the strong invasiveness of S. aureus in muscle cells, a property not shared by NSTI-GAS isolates.
Insights
Staphylococcus aureus (SA) readily invades muscle cells, unlike group A Streptococcus (GAS). This strong invasiveness in muscle cells contributes to the severity of SA necrotizing soft tissue infections (NSTIs).
Area of Science:
- Microbiology
- Infectious Diseases
- Cell Biology
Background:
- Necrotizing soft tissue infections (NSTIs) often involve deep fascia and muscle necrosis.
- Group A Streptococcus (GAS) and Staphylococcus aureus (SA) are key causative agents of NSTIs.
Purpose of the Study:
- To compare the pathogenicity of GAS and SA in muscle cells versus keratinocytes.
- To investigate the adhesion and invasion mechanisms of NSTI-associated GAS and SA isolates.
Main Methods:
- Assessed adhesion and invasion of NSTI-GAS and NSTI-SA isolates in human keratinocytes and myoblasts.
- Utilized bloodstream infection SA (BSI-SA) and coagulase-negative staphylococci (CNS) as controls.
- Analyzed cytotoxicity, gene transcript levels (psmα, RNAIII), and α5β1 integrin expression.
Main Results:
- NSTI-SA and BSI-SA showed significantly higher internalization into human myoblasts compared to keratinocytes.
- S. aureus internalization exceeded 30% in myoblasts, with higher infection rates than in keratinocytes.
- NSTI-SA exhibited greater myoblast cytotoxicity, linked to elevated psmα and RNAIII transcripts and α5β1 integrin expression.
Conclusions:
- The strong invasiveness of S. aureus in muscle cells is a key factor in NSTI severity.
- This muscle cell invasiveness is a characteristic not observed with GAS isolates.
- The FnbpAB-integrin α5β1 pathway plays a major role in S. aureus internalization into myoblasts.
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