Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis
Abstract Septic arthritis, primarily caused by Staphylococcus aureus, poses a significant risk of both mortality and morbidity due to its aggressive nature. The nuc1-encoded thermonuclease NucA of S. aureus degrades extracellular DNA/RNA, allowing the pathogen to escape neutrophil extracellular trap...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07920-4 |
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| author | Ningna Li Meghshree Vinod Deshmukh Filiz Sahin Nourhane Hafza Aparna Viswanathan Ammanath Sabrina Ehnert Andreas Nüssler Alexander N. R. Weber Tao Jin Friedrich Götz |
| author_facet | Ningna Li Meghshree Vinod Deshmukh Filiz Sahin Nourhane Hafza Aparna Viswanathan Ammanath Sabrina Ehnert Andreas Nüssler Alexander N. R. Weber Tao Jin Friedrich Götz |
| author_sort | Ningna Li |
| collection | DOAJ |
| description | Abstract Septic arthritis, primarily caused by Staphylococcus aureus, poses a significant risk of both mortality and morbidity due to its aggressive nature. The nuc1-encoded thermonuclease NucA of S. aureus degrades extracellular DNA/RNA, allowing the pathogen to escape neutrophil extracellular traps (NETs) and maintain the infection unabated. Here we show that in the mouse model for hematogenous septic arthritis, the Δnuc1 mutant is much less pathogenic and the severity of clinical septic arthritis is markedly reduced, including decreased weight loss, lower kidney bacterial load, reduced bone erosion, and much less IL-6 production. In vitro, S. aureus genomic DNA induces a robust TNF-α response in macrophage-like RAW 264.7 cells abrogated when the DNA is degraded by NucA. Moreover, the wild type induces high levels of TNF-α, IL-10, and IL-6 in neutrophils and osteoblast-like SAOS-2 cells, respectively. NucA exacerbates septic arthritis by increasing extracellular and intracellular survival of bacteria. |
| format | Article |
| id | doaj-art-efb3f93e500a4f7c9cdbf1fc7a7a49cd |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-efb3f93e500a4f7c9cdbf1fc7a7a49cd2025-08-20T02:12:02ZengNature PortfolioCommunications Biology2399-36422025-04-018111210.1038/s42003-025-07920-4Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritisNingna Li0Meghshree Vinod Deshmukh1Filiz Sahin2Nourhane Hafza3Aparna Viswanathan Ammanath4Sabrina Ehnert5Andreas Nüssler6Alexander N. R. Weber7Tao Jin8Friedrich Götz9Interfaculty Institute of Microbiology and Infection Medicine, University of TübingenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgSiegfried Weller Institute for trauma research, BG Unfallklinik Tübingen, University of TübingenInterfaculty Institute of Microbiology and Infection Medicine, University of TübingenInterfaculty Institute of Microbiology and Infection Medicine, University of TübingenSiegfried Weller Institute for trauma research, BG Unfallklinik Tübingen, University of TübingenSiegfried Weller Institute for trauma research, BG Unfallklinik Tübingen, University of TübingenInterfaculty Institute for Cell Biology, Department of Immunology, Section Innate Immunity, University of TübingenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgInterfaculty Institute of Microbiology and Infection Medicine, University of TübingenAbstract Septic arthritis, primarily caused by Staphylococcus aureus, poses a significant risk of both mortality and morbidity due to its aggressive nature. The nuc1-encoded thermonuclease NucA of S. aureus degrades extracellular DNA/RNA, allowing the pathogen to escape neutrophil extracellular traps (NETs) and maintain the infection unabated. Here we show that in the mouse model for hematogenous septic arthritis, the Δnuc1 mutant is much less pathogenic and the severity of clinical septic arthritis is markedly reduced, including decreased weight loss, lower kidney bacterial load, reduced bone erosion, and much less IL-6 production. In vitro, S. aureus genomic DNA induces a robust TNF-α response in macrophage-like RAW 264.7 cells abrogated when the DNA is degraded by NucA. Moreover, the wild type induces high levels of TNF-α, IL-10, and IL-6 in neutrophils and osteoblast-like SAOS-2 cells, respectively. NucA exacerbates septic arthritis by increasing extracellular and intracellular survival of bacteria.https://doi.org/10.1038/s42003-025-07920-4 |
| spellingShingle | Ningna Li Meghshree Vinod Deshmukh Filiz Sahin Nourhane Hafza Aparna Viswanathan Ammanath Sabrina Ehnert Andreas Nüssler Alexander N. R. Weber Tao Jin Friedrich Götz Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis Communications Biology |
| title | Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis |
| title_full | Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis |
| title_fullStr | Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis |
| title_full_unstemmed | Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis |
| title_short | Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis |
| title_sort | staphylococcus aureus thermonuclease nuca is a key virulence factor in septic arthritis |
| url | https://doi.org/10.1038/s42003-025-07920-4 |
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