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

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

Wed, 24/04/2019

Publication

Publication by the International Center for Infectiology Research (CIRI) in The Journal of Infectious Diseases on April 19, 2019.

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.

Subject(s)
Keywords