CRISPR-dependent endogenous gene regulation is required for virulence in piscine Streptococcus agalactiae
Autor: | Qing Cao, Guangjin Liu, Yongjie Liu, Yuhao Dong, Meng Nie, Hao Huang, Chengping Lu, Mingguo Jiang, Ke Ma |
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Rok vydání: | 2021 |
Předmět: |
Epidemiology
Immunology Virulence Endogeny CovR/S Biology medicine.disease_cause Microbiology Streptococcus agalactiae Fish Diseases Mice Bacterial Proteins Streptococcal Infections Virology Drug Discovery medicine Animals CRISPR Clustered Regularly Interspaced Short Palindromic Repeats lipoprotein Sag0671 Genetics Perforin Fishes Palindrome Gene Expression Regulation Bacterial General Medicine Mice Inbred C57BL Infectious Diseases Female Parasitology Mobile genetic elements Research Article |
Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
ISSN: | 2222-1751 |
Popis: | The clustered regularly interspaced palindromic repeats (CRISPR)-Cas (CRISPR-associated) system is a prokaryotic defence against invading mobile genetic elements, such as bacteriophages or exogenous plasmids. Beyond this, this system has been shown to play an important role in controlling the virulence of some bacterial pathogens. Streptococcus agalactiae strain GD201008-001, a causative agent of septicemia and meningitis in tilapia, contains a single type II CRISPR-Cas system with Cas9 as a signature protein. In this study, we found that the deletion of CRISPR significantly reduced adhesion, invasion, cytotoxicity and haemolysis, and caused severely attenuated virulence in the piscine S. agalactiae strain. RNA-Seq identified 236 endogenous genes regulated by CRISPR, with 159 genes upregulated and 77 genes downregulated. The resulting change in gene transcription by CRISPR was much more pronounced than that by cas9 in this bacterium, indicating CRISPR-mediated endogenous gene regulation was mostly independently of cas9. Subsequent studies showed that CovR/S two-component system was transcriptionally upregulated due to CRISPR deletion, which repressed the expression of the cylE gene coding for a cytolytic toxin, and thus decreased the activity of β-haemolysin/cytolysin. However, upregulation of CovR/S was not the contributor to the attenuation phenotype of ΔCRISPR. Further, we demonstrated that CRISPR is capable of repressing the expression of Toll-like receptor 2 (TLR2)-activating lipoprotein Sag0671 and thus dampens the innate immune response. This study revealed that the CRISPR system of S. agalactiae exhibited extraordinary potential capability in the regulation of endogenous transcripts, which contributes to bacterial innate immune evasion and virulence. |
Databáze: | OpenAIRE |
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