Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning
The virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role o...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2228657 |
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| author | Jinlong Yu Mingzhang Li Jin Wang Musha Hamushan Feng Jiang Boyong Wang Yujie Hu Pei Han Jin Tang Geyong Guo Hao Shen |
| author_facet | Jinlong Yu Mingzhang Li Jin Wang Musha Hamushan Feng Jiang Boyong Wang Yujie Hu Pei Han Jin Tang Geyong Guo Hao Shen |
| author_sort | Jinlong Yu |
| collection | DOAJ |
| description | The virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role of sRNA from 506 S. aureus RNA-seq datasets using independent component analysis (ICA). We found that a previously neglected sRNA, Sau-41, functions in the Agr system. Sau-41 is located within the PSMα operon and controlled by the Agr system. It was predicted to share 22-base complementarity with RNAIII, a major regulator of S. aureus virulence. The EMSA results demonstrated that Sau-41 directly binds to RNAIII. Furthermore, our results found that Sau-41 is capable of repressing S. aureus haemolysin activity by downregulating α-haemolysin and δ-toxin. The repression of α-haemolysin was attributed to the competition between the 5’ UTR of hla and Sau-41 for binding RNAIII. We observed that Sau-41 mitigated S. aureus virulence in an orthopaedic implant infection mouse model and alleviated osteolysis. Together, our results indicate that Sau-41 is a virulence-regulating RNA and suggest that Sau-41 might be involved in a negative feedback mechanism to control the Agr system. This work is a demonstration of using ICA in sRNA identification by mining high-throughput data and could be extended to other organisms as well. |
| format | Article |
| id | doaj-art-a9deeb09699a4299879ef969ed89a834 |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-a9deeb09699a4299879ef969ed89a8342025-08-20T03:27:33ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2228657Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learningJinlong Yu0Mingzhang Li1Jin Wang2Musha Hamushan3Feng Jiang4Boyong Wang5Yujie Hu6Pei Han7Jin Tang8Geyong Guo9Hao Shen10Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role of sRNA from 506 S. aureus RNA-seq datasets using independent component analysis (ICA). We found that a previously neglected sRNA, Sau-41, functions in the Agr system. Sau-41 is located within the PSMα operon and controlled by the Agr system. It was predicted to share 22-base complementarity with RNAIII, a major regulator of S. aureus virulence. The EMSA results demonstrated that Sau-41 directly binds to RNAIII. Furthermore, our results found that Sau-41 is capable of repressing S. aureus haemolysin activity by downregulating α-haemolysin and δ-toxin. The repression of α-haemolysin was attributed to the competition between the 5’ UTR of hla and Sau-41 for binding RNAIII. We observed that Sau-41 mitigated S. aureus virulence in an orthopaedic implant infection mouse model and alleviated osteolysis. Together, our results indicate that Sau-41 is a virulence-regulating RNA and suggest that Sau-41 might be involved in a negative feedback mechanism to control the Agr system. This work is a demonstration of using ICA in sRNA identification by mining high-throughput data and could be extended to other organisms as well.https://www.tandfonline.com/doi/10.1080/21505594.2023.2228657machine learningStaphylococcus aureussRNAindependent component analysisRNA-seq |
| spellingShingle | Jinlong Yu Mingzhang Li Jin Wang Musha Hamushan Feng Jiang Boyong Wang Yujie Hu Pei Han Jin Tang Geyong Guo Hao Shen Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning Virulence machine learning Staphylococcus aureus sRNA independent component analysis RNA-seq |
| title | Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning |
| title_full | Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning |
| title_fullStr | Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning |
| title_full_unstemmed | Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning |
| title_short | Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning |
| title_sort | identification of staphylococcus aureus virulence modulating rna from transcriptomics data with machine learning |
| topic | machine learning Staphylococcus aureus sRNA independent component analysis RNA-seq |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2228657 |
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