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 ( ), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that sev...

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Bibliographic Details
Published in:Frontiers in microbiology 2021-12, Vol.12, p.774492-774492
Main Authors: Yang, Fan, Xu, Lingqing, Liang, Lujie, Liang, Wanfei, Li, Jiachen, Lin, Daixi, Dai, Min, Zhou, Dianrong, Li, Yaxin, Chen, Yong, Zhao, Hui, Tian, Guo-Bao, Feng, Siyuan
Format: Article
Language:English
Subjects:
envelope integrity
immunoregulation
Microbiology
Mycobacterium
oxidative stress
type III-A CRISPR-Cas
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Summary:Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria's own genes. Although ( ), 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 ( ∼ , , ) were upregulated in 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 ( ype III-A RISPR as system, including , , and - ) 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 and . 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.
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2021.774492