The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress
Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.774492/full |
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| author | Fan Yang Lingqing Xu Lujie Liang Lujie Liang Wanfei Liang Wanfei Liang Jiachen Li Jiachen Li Daixi Lin Daixi Lin Min Dai Dianrong Zhou Dianrong Zhou Yaxin Li Yaxin Li Yong Chen Hui Zhao Guo-bao Tian Guo-bao Tian Siyuan Feng Siyuan Feng |
| author_facet | Fan Yang Lingqing Xu Lujie Liang Lujie Liang Wanfei Liang Wanfei Liang Jiachen Li Jiachen Li Daixi Lin Daixi Lin Min Dai Dianrong Zhou Dianrong Zhou Yaxin Li Yaxin Li Yong Chen Hui Zhao Guo-bao Tian Guo-bao Tian Siyuan Feng Siyuan Feng |
| author_sort | Fan Yang |
| collection | DOAJ |
| description | Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy. |
| first_indexed | 2024-12-17T21:03:52Z |
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| id | doaj.art-f78b2fef80724ca1b4c5e02880d0b19c |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-17T21:03:52Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f78b2fef80724ca1b4c5e02880d0b19c2022-12-21T21:32:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-12-011210.3389/fmicb.2021.774492774492The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative StressFan Yang0Lingqing Xu1Lujie Liang2Lujie Liang3Wanfei Liang4Wanfei Liang5Jiachen Li6Jiachen Li7Daixi Lin8Daixi Lin9Min Dai10Dianrong Zhou11Dianrong Zhou12Yaxin Li13Yaxin Li14Yong Chen15Hui Zhao16Guo-bao Tian17Guo-bao Tian18Siyuan Feng19Siyuan Feng20Department of Microbiology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, ChinaDepartment of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, ChinaGuangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, ChinaType I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy.https://www.frontiersin.org/articles/10.3389/fmicb.2021.774492/fulltype III-A CRISPR-CasMycobacteriumenvelope integrityoxidative stressimmunoregulation |
| spellingShingle | Fan Yang Lingqing Xu Lujie Liang Lujie Liang Wanfei Liang Wanfei Liang Jiachen Li Jiachen Li Daixi Lin Daixi Lin Min Dai Dianrong Zhou Dianrong Zhou Yaxin Li Yaxin Li Yong Chen Hui Zhao Guo-bao Tian Guo-bao Tian Siyuan Feng Siyuan Feng The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress Frontiers in Microbiology type III-A CRISPR-Cas Mycobacterium envelope integrity oxidative stress immunoregulation |
| title | The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress |
| title_full | The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress |
| title_fullStr | The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress |
| title_full_unstemmed | The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress |
| title_short | The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress |
| title_sort | involvement of mycobacterium type iii a crispr cas system in oxidative stress |
| topic | type III-A CRISPR-Cas Mycobacterium envelope integrity oxidative stress immunoregulation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.774492/full |
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