Cell research, 2016-12, Vol.26 (12), p.1273-1287
2016
Details
- Autor(en) / Beteiligte
- Titel
- Type I CRISPR-Cas targets endogenous genes and regulates virulence to evade mammalian host immunity
- Ist Teil von
- Cell research, 2016-12, Vol.26 (12), p.1273-1287
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- Clustered regularly interspaced short palindromic repeats （CRISPR）-CRISPR-associated （Cas） systems in bac- teria and archaea provide adaptive immunity against invading foreign nucleic acids. Previous studies suggest that certain bacteria employ their Type II CRISPR-Cas systems to target their own genes, thus evading host immunity. However, whether other CRISPR-Cas systems have similar functions during bacterial invasion of host cells remains unknown. Here we identify a novel role for Type I CRISPR-Cas systems in evading host defenses in Pseudomonas aeruginosa strain UCBPP-PA14. The Type I CRISPR-Cas system of PAl4 targets the mRNA of the bacterial quo- rum-sensing regulator LasR to dampen the recognition by toll-like receptor 4, thus diminishing the pro-inflammatory responses of the host in cell and mouse models. Mechanistically, this nuclease-mediated RNA degradation requires a ＂5＇-GGN-3＇＂ recognition motif in the target mRNA, and HD and DExD/H domains in Cas3 of the Type I CRIS- PR-Cas system. As LasR and Type I CRISPR-Cas systems are ubiquitously present in bacteria, our findings elucidate an important common mechanism underlying bacterial virulence.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1001-0602eISSN: 1748-7838DOI: 10.1038/cr.2016.135Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5143421
- Format
- –
- Schlagworte
- Adaptive immunity, Adaptive systems, Animal models, Animals, Archaea, Bacteria, Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Base Sequence, Biodegradation, Bronchoalveolar Lavage Fluid - chemistry, Bronchoalveolar Lavage Fluid - cytology, Cell culture, Cells, Cultured, CRISPR, CRISPR-Associated Proteins - chemistry, CRISPR-Associated Proteins - genetics, CRISPR-Cas Systems - genetics, Domains, Female, Gene Targeting, Genes, Immunity, Immunity, Innate, Inflammation, Inflammation - pathology, Lung - microbiology, Lung - pathology, Macrophages - cytology, Macrophages - immunology, Macrophages - metabolism, Mice, Mice, Inbred C57BL, mRNA, Nuclease, Nucleic acids, Nucleotide Motifs, Original, Pathogens, Pseudomonas aeruginosa, Pseudomonas aeruginosa - genetics, Pseudomonas aeruginosa - metabolism, Pseudomonas aeruginosa - pathogenicity, Pseudomonas Infections - microbiology, Pseudomonas Infections - mortality, Pseudomonas Infections - pathology, Pseudomonas Infections - veterinary, Ribonucleic acid, RNA, RNA, Messenger - metabolism, Signal Transduction, Target recognition, TLR4 protein, Toll-like receptors, Trans-Activators - genetics, Trans-Activators - metabolism, Virulence, Virulence - genetics