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Streptococcus pyogenes NAD+-Glycohydrolase Reduces Skeletal Muscle βNAD+ Levels Independently of Streptolysin O
| Content Provider | MDPI |
|---|---|
| Author | McIndoo, Eric R. Price, Emily Lamb, Cheri L. Dayton, Christopher S. Bayer, Clifford R. Stevens, Dennis L. Bryant, Amy E. Hobdey, Sarah E. |
| Copyright Year | 2022 |
| Description | Necrotizing soft tissue infections caused by Streptococcus pyogenes (group A streptococcus [GAS]) are characterized by rapid and extensive necrosis of fascia and muscle. Molecular epidemiological studies have demonstrated a positive correlation between GAS isolates that cause invasive infections and the production of S. pyogenes NAD+-glycohydrolase (SPN), an NADase secreted by GAS, but the effect of SPN on muscle cells has not been described. Thus, using standard βNAD+ and ATP quantification assays, we investigated the effects of SPN on cultured human skeletal muscle cell (SkMC) βNAD+ and ATP with and without streptolysin O (SLO)–a secreted cholesterol-dependent cytolysin known to act synergistically with SPN. We found that culture supernatants from GAS strains producing SLO and SPN depleted intracellular βNAD+ and ATP, while exotoxins from a GAS strain producing SLO and an enzymatically-inactive form of SPN had no effect on βNAD+ or ATP. Addition of purified, enzymatically-active SPN to NADase-negative culture supernatants or sterile media reconstituted βNAD+ depletion but had no effect ATP levels. Further, SPN-mediated βNAD+ depletion could be augmented by SLO or the homologous cholesterol-dependent cytolysin, perfringolysin O (PFO). Remarkably, SPN-mediated βNAD+ depletion was SkMC-specific, as purified SPN had minimal effect on epithelial cell βNAD+. Taken together, this study identifies a previously unrecognized role for SPN as a major disruptor of skeletal muscle βNAD+. Such activity could contribute to the rapid and widespread myonecrosis characteristic of severe GAS soft tissue infections. |
| Starting Page | 1476 |
| e-ISSN | 20762607 |
| DOI | 10.3390/microorganisms10071476 |
| Journal | Microorganisms |
| Issue Number | 7 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-07-21 |
| Access Restriction | Open |
| Subject Keyword | Microorganisms Microbiology Streptococcus Pyogenes Bacterial Toxins Pathology Skeletal Muscle |
| Content Type | Text |
| Resource Type | Article |
