Type I CRISPR-Cas targets endogenous genes and regulates virulence to evade mammalian host immunity  

作　　者：Rongpeng Li Lizhu Fang Shirui Tan Min Yu Xuefeng Li Sisi He Yuquan Wei Guoping Li Jianxin Jiang Min Wu 

机构地区：[1]Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA [2]State Key Laboratory ofBiotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy,Chengdu, Siehuan 610041, China [3]Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Southwest MedicalUniversity, Luzhou, Sichuan 646004, China [4]State Key Laboratory of Trauma, Burns and Combined Injury, Institute of SurgeryResearch, Daping Hospital, Third Military Medical University, Chongqing 400042, China

出　　处：《Cell Research》2016年第12期1273-1287,共15页细胞研究（英文版）

摘　　要：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.

关 键 词：type I CRISPR Pseudomonas aeruginosa quorum sensing LasR endogenous targeting 

分 类 号：Q[生物学]