CdpR Inhibits CRISPR-Cas Adaptive Immunity to Lower Anti-viral Defense while Avoiding Self-Reactivity
Ping Lin,
Qinqin Pu,
Guanwang Shen,
Rongpeng Li,
Kai Guo,
Chuanmin Zhou,
Haihua Liang,
Jianxin Jiang,
Min Wu
Affiliations
Ping Lin
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing 400042, P. R. China; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Qinqin Pu
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Guanwang Shen
Biological Science Research Center, Southwest University, Chongqing 400715, P. R. China
Rongpeng Li
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA; Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China
Kai Guo
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Chuanmin Zhou
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Haihua Liang
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, P. R. China; Corresponding author
Jianxin Jiang
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing 400042, P. R. China; Corresponding author
Min Wu
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA; Corresponding author
Summary: CRISPR-Cas systems as adaptive immunity in bacteria and archaea battle against bacteriophages. However, little is known how CRISPR-Cas systems are precisely regulated to effectively eliminate intruders while not inducing self-reactivity. Here, we identify intrinsic negative modulator of CRISPR-Cas that influences interference and adaptation functions. LasI/RhlI-derived autoinducers activate cas operon by enhancing the binding of virulence factor regulator (Vfr) cis-response elements to cas1 promoter, whereas CdpR represses this intracellular signaling and blocks transcription of cas operon. Importantly, inhibition of Vfr reduces cas1 expression and impairs immunization and immune memory mediated by CRISPR-Cas, leading to more severe phage infection but lower self-targeting activities. In addition, CdpR-mediated LasI/RhlI/Vfr intracellular signaling represses cleavage of bacterial endogenous sequences by impeding Cas3 RNA cleavage activity. Thus, CdpR renders important inhibitory effects on CRISPR-Cas systems to avoid possible self-reactivity but potentially heightening infection risk. Our study provides insight into fine regulation of CRISPR-Cas systems for maintaining homeostasis. : Biological Sciences; Molecular Biology; Molecular Microbiology Subject Areas: Biological Sciences, Molecular Biology, Molecular Microbiology
