Necrotizing Soft Tissue Infections S.aureus - but not S.pyogenes- isolates display high rate of internalization and cytotoxicity toward human myoblasts.

, , , , , , , Stephanie Duguez, , , , , ,

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Abstract

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 SA for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed on these cells, Bloodstream infections (BSI-SA) and non-invasive 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. SA 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 psm and RNAIII transcripts in NSTI-SA. However, the two 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. CONCLUSION: Our findings suggest the contribution of SA to NSTI severity by a prominent SA invasiveness in muscle cells, a property not shared by NSTI-GAS isolates.
LanguageEnglish
Article numberdoi: 10.1093/infdis/jiz167
JournalJournal of Infectious Diseases
DOIs
Publication statusE-pub ahead of print - 19 Apr 2019

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Soft Tissue Infections
Myoblasts
Staphylococcus aureus
Integrins
Muscles
Fascia
Staphylococcus
Keratinocytes
Muscle Cells
Virulence
Necrosis

Keywords

  • Staphylococcus aureus
  • Streptococcus
  • muscle cells
  • necrotizing soft tissue infections
  • pyogenes

Cite this

@article{b35d60ccb72a49d7a6a8217f73990930,
title = "Necrotizing Soft Tissue Infections S.aureus - but not S.pyogenes- isolates display high rate of internalization and cytotoxicity toward human myoblasts.",
abstract = "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 SA for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed on these cells, Bloodstream infections (BSI-SA) and non-invasive 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. SA 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 psm and RNAIII transcripts in NSTI-SA. However, the two 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. CONCLUSION: Our findings suggest the contribution of SA to NSTI severity by a prominent SA invasiveness in muscle cells, a property not shared by NSTI-GAS isolates.",
keywords = "Staphylococcus aureus, Streptococcus, muscle cells, necrotizing soft tissue infections, pyogenes",
author = "Stephanie Duguez",
year = "2019",
month = "4",
day = "19",
doi = "10.1093/infdis/jiz167",
language = "English",

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T1 - Necrotizing Soft Tissue Infections S.aureus - but not S.pyogenes- isolates display high rate of internalization and cytotoxicity toward human myoblasts.

AU - Duguez, Stephanie

PY - 2019/4/19

Y1 - 2019/4/19

N2 - 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 SA for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed on these cells, Bloodstream infections (BSI-SA) and non-invasive 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. SA 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 psm and RNAIII transcripts in NSTI-SA. However, the two 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. CONCLUSION: Our findings suggest the contribution of SA to NSTI severity by a prominent SA invasiveness in muscle cells, a property not shared by NSTI-GAS isolates.

AB - 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 SA for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed on these cells, Bloodstream infections (BSI-SA) and non-invasive 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. SA 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 psm and RNAIII transcripts in NSTI-SA. However, the two 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. CONCLUSION: Our findings suggest the contribution of SA to NSTI severity by a prominent SA invasiveness in muscle cells, a property not shared by NSTI-GAS isolates.

KW - Staphylococcus aureus

KW - Streptococcus

KW - muscle cells

KW - necrotizing soft tissue infections

KW - pyogenes

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DO - 10.1093/infdis/jiz167

M3 - Article

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