title: Type I CRISPR-Cas targets endogenous genes and regulates virulence to evade mammalian host immunity.
abstract: Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems in bacteria 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 PA14 targets the mRNA of the bacterial quorum-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 CRISPR-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.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.
authors.forename: Rongpeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.
authors.forename: Shirui
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646004, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9061, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D064130:CRISPR-Associated Proteins / Q000737:chemistry / Q000235:genetics; D064113:CRISPR-Cas Systems / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D018390:Gene Targeting; D007113:Immunity, Innate; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D059372:Nucleotide Motifs; D011552:Pseudomonas Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology / Q000662:veterinary; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D064130:CRISPR-Associated Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D012333:RNA, Messenger; D015534:Trans-Activators