The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus
ABSTRACTIn many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2171641 |
| _version_ | 1797367191096524800 |
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| author | Feifei Chen Hongxia Di Yanhui Wang Chao Peng Rongrong Chen Huiwen Pan Cai-Guang Yang Haihua Liang Lefu Lan |
| author_facet | Feifei Chen Hongxia Di Yanhui Wang Chao Peng Rongrong Chen Huiwen Pan Cai-Guang Yang Haihua Liang Lefu Lan |
| author_sort | Feifei Chen |
| collection | DOAJ |
| description | ABSTRACTIn many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus. |
| first_indexed | 2024-03-08T17:13:43Z |
| format | Article |
| id | doaj.art-4e9609ff32474408999f647ca6ed988a |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-03-08T17:13:43Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-4e9609ff32474408999f647ca6ed988a2024-01-03T17:26:57ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2171641The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureusFeifei Chen0Hongxia Di1Yanhui Wang2Chao Peng3Rongrong Chen4Huiwen Pan5Cai-Guang Yang6Haihua Liang7Lefu Lan8College of Life Science, Northwest University, Xi’an, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaNational Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai, ChinaHangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, ChinaHangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaCollege of Life Science, Northwest University, Xi’an, ChinaCollege of Life Science, Northwest University, Xi’an, ChinaABSTRACTIn many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus.https://www.tandfonline.com/doi/10.1080/21505594.2023.2171641Staphylococcus aureusSortase Aprotein phosphorylationvirulence |
| spellingShingle | Feifei Chen Hongxia Di Yanhui Wang Chao Peng Rongrong Chen Huiwen Pan Cai-Guang Yang Haihua Liang Lefu Lan The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus Virulence Staphylococcus aureus Sortase A protein phosphorylation virulence |
| title | The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus |
| title_full | The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus |
| title_fullStr | The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus |
| title_full_unstemmed | The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus |
| title_short | The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus |
| title_sort | enzyme activity of sortase a is regulated by phosphorylation in staphylococcus aureus |
| topic | Staphylococcus aureus Sortase A protein phosphorylation virulence |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2171641 |
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