The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling
Summary: The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Stap...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000524 |
| _version_ | 1797903384420810752 |
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| author | Mariya I. Goncheva Richard M. Gibson Ainslie C. Shouldice Jimmy D. Dikeakos David E. Heinrichs |
| author_facet | Mariya I. Goncheva Richard M. Gibson Ainslie C. Shouldice Jimmy D. Dikeakos David E. Heinrichs |
| author_sort | Mariya I. Goncheva |
| collection | DOAJ |
| description | Summary: The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Staphylococcus aureus. Here, we describe the development of an in vitro co-infection model where both viral and bacterial replication kinetics may be examined. We demonstrate CoV-2 infection does not alter bacterial interactions with host epithelial cells. In contrast, S. aureus enhances CoV-2 replication by 10- to 15-fold. We identify this pro-viral activity is due to the S. aureus iron-regulated surface determinant A (IsdA) protein and demonstrate IsdA modifies host transcription. We find that IsdA alters Janus Kinase – Signal Transducer and Activator of Transcription (JAK-STAT) signaling, by affecting JAK2-STAT3 levels, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions between host cells, CoV-2 and S. aureus during co-infection. |
| first_indexed | 2024-04-10T09:32:03Z |
| format | Article |
| id | doaj.art-7937bbc7a281482e8c3fe1e0773ff74a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:32:03Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7937bbc7a281482e8c3fe1e0773ff74a2023-02-19T04:26:47ZengElsevieriScience2589-00422023-02-01262105975The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signalingMariya I. Goncheva0Richard M. Gibson1Ainslie C. Shouldice2Jimmy D. Dikeakos3David E. Heinrichs4Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada; Corresponding authorImPaKT Laboratory, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada; Corresponding authorSummary: The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Staphylococcus aureus. Here, we describe the development of an in vitro co-infection model where both viral and bacterial replication kinetics may be examined. We demonstrate CoV-2 infection does not alter bacterial interactions with host epithelial cells. In contrast, S. aureus enhances CoV-2 replication by 10- to 15-fold. We identify this pro-viral activity is due to the S. aureus iron-regulated surface determinant A (IsdA) protein and demonstrate IsdA modifies host transcription. We find that IsdA alters Janus Kinase – Signal Transducer and Activator of Transcription (JAK-STAT) signaling, by affecting JAK2-STAT3 levels, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions between host cells, CoV-2 and S. aureus during co-infection.http://www.sciencedirect.com/science/article/pii/S2589004223000524Biological sciencesMicrobiologyVirology |
| spellingShingle | Mariya I. Goncheva Richard M. Gibson Ainslie C. Shouldice Jimmy D. Dikeakos David E. Heinrichs The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling iScience Biological sciences Microbiology Virology |
| title | The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling |
| title_full | The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling |
| title_fullStr | The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling |
| title_full_unstemmed | The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling |
| title_short | The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling |
| title_sort | staphylococcus aureus protein isda increases sars cov 2 replication by modulating jak stat signaling |
| topic | Biological sciences Microbiology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000524 |
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