Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition
ABSTRACTStreptococcus suis type 2 (SS2), a major emerging/re-emerging zoonotic pathogen found in humans and pigs, can cause severe clinical infections, and pose public health issues. Our previous studies recognized peptidyl-prolyl isomerase (PrsA) as a critical virulence factor promoting SS2 pathoge...
| 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/10.1080/21505594.2023.2249779 |
| _version_ | 1797367146188111872 |
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| author | Xiaowu Jiang Guijun Yu Lexin Zhu Abubakar Siddique Dongbo Zhan Linhua Zhou Min Yue |
| author_facet | Xiaowu Jiang Guijun Yu Lexin Zhu Abubakar Siddique Dongbo Zhan Linhua Zhou Min Yue |
| author_sort | Xiaowu Jiang |
| collection | DOAJ |
| description | ABSTRACTStreptococcus suis type 2 (SS2), a major emerging/re-emerging zoonotic pathogen found in humans and pigs, can cause severe clinical infections, and pose public health issues. Our previous studies recognized peptidyl-prolyl isomerase (PrsA) as a critical virulence factor promoting SS2 pathogenicity. PrsA contributed to cell death and operated as a pro-inflammatory effector. However, the molecular pathways through which PrsA contributes to cell death are poorly understood. Here in this study, we prepared the recombinant PrsA protein and found that pyroptosis and necroptosis were involved in cell death stimulated by PrsA. Specific pyroptosis and necroptosis signalling inhibitors could significantly alleviate the fatal effect. Cleaved caspase-1 and IL-1β in pyroptosis with phosphorylated MLKL proteins in necroptosis pathways, respectively, were activated after PrsA stimulation. Truncated protein fragments of enzymatic PPIase domain (PPI), N-terminal (NP), and C-terminal (PC) domains fused with PPIase, were expressed and purified. PrsA flanking N- or C-terminal but not enzymatic PPIase domain was found to be critical for PrsA function in inducing cell death and inflammation. Additionally, PrsA protein could be anchored on the cell surface to interact with host cells. However, Toll-like receptor 2 (TLR2) was not implicated in cell death and recognition of PrsA. PAMPs of PrsA could not promote TLR2 activation, and no rescued phenotypes of death were shown in cells blocking of TLR2 receptor or signal-transducing adaptor of MyD88. Overall, these data, for the first time, advanced our perspective on PrsA function and elucidated that PrsA-induced cell death requires its flanking N- or C-terminal domain but is dispensable for recognizing TLR2. Further efforts are still needed to explore the precise molecular mechanisms of PrsA-inducing cell death and, therefore, contribution to SS2 pathogenicity. |
| first_indexed | 2024-03-08T17:14:09Z |
| format | Article |
| id | doaj.art-b7ac72b5575b426787dfca512b553bb0 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-03-08T17:14:09Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-b7ac72b5575b426787dfca512b553bb02024-01-03T17:26:57ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2249779Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognitionXiaowu Jiang0Guijun Yu1Lexin Zhu2Abubakar Siddique3Dongbo Zhan4Linhua Zhou5Min Yue6College of Medicine, Yichun University, Yichun, Jiangxi, ChinaCollege of Medicine, Yichun University, Yichun, Jiangxi, ChinaCollege of Medicine, Yichun University, Yichun, Jiangxi, ChinaHainan Institute of Zhejiang University, Sanya, ChinaCollege of Medicine, Yichun University, Yichun, Jiangxi, ChinaCollege of Medicine, Yichun University, Yichun, Jiangxi, ChinaHainan Institute of Zhejiang University, Sanya, ChinaABSTRACTStreptococcus suis type 2 (SS2), a major emerging/re-emerging zoonotic pathogen found in humans and pigs, can cause severe clinical infections, and pose public health issues. Our previous studies recognized peptidyl-prolyl isomerase (PrsA) as a critical virulence factor promoting SS2 pathogenicity. PrsA contributed to cell death and operated as a pro-inflammatory effector. However, the molecular pathways through which PrsA contributes to cell death are poorly understood. Here in this study, we prepared the recombinant PrsA protein and found that pyroptosis and necroptosis were involved in cell death stimulated by PrsA. Specific pyroptosis and necroptosis signalling inhibitors could significantly alleviate the fatal effect. Cleaved caspase-1 and IL-1β in pyroptosis with phosphorylated MLKL proteins in necroptosis pathways, respectively, were activated after PrsA stimulation. Truncated protein fragments of enzymatic PPIase domain (PPI), N-terminal (NP), and C-terminal (PC) domains fused with PPIase, were expressed and purified. PrsA flanking N- or C-terminal but not enzymatic PPIase domain was found to be critical for PrsA function in inducing cell death and inflammation. Additionally, PrsA protein could be anchored on the cell surface to interact with host cells. However, Toll-like receptor 2 (TLR2) was not implicated in cell death and recognition of PrsA. PAMPs of PrsA could not promote TLR2 activation, and no rescued phenotypes of death were shown in cells blocking of TLR2 receptor or signal-transducing adaptor of MyD88. Overall, these data, for the first time, advanced our perspective on PrsA function and elucidated that PrsA-induced cell death requires its flanking N- or C-terminal domain but is dispensable for recognizing TLR2. Further efforts are still needed to explore the precise molecular mechanisms of PrsA-inducing cell death and, therefore, contribution to SS2 pathogenicity.https://www.tandfonline.com/doi/10.1080/21505594.2023.2249779Streptococcus suis type 2PrsApyroptosisnecroptosisTLR2 |
| spellingShingle | Xiaowu Jiang Guijun Yu Lexin Zhu Abubakar Siddique Dongbo Zhan Linhua Zhou Min Yue Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition Virulence Streptococcus suis type 2 PrsA pyroptosis necroptosis TLR2 |
| title | Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition |
| title_full | Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition |
| title_fullStr | Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition |
| title_full_unstemmed | Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition |
| title_short | Flanking N- and C-terminal domains of PrsA in Streptococcus suis type 2 are crucial for inducing cell death independent of TLR2 recognition |
| title_sort | flanking n and c terminal domains of prsa in streptococcus suis type 2 are crucial for inducing cell death independent of tlr2 recognition |
| topic | Streptococcus suis type 2 PrsA pyroptosis necroptosis TLR2 |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2249779 |
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