title: Pseudomonas aeruginosa Oligoribonuclease Contributes to Tolerance to Ciprofloxacin by Regulating Pyocin Biosynthesis.
abstract: Bacterial oligoribonuclease (Orn) is a conserved 3'-to-5' exonuclease. InPseudomonas aeruginosa, it has been demonstrated that Orn plays a major role in the hydrolysis of pGpG, which is required for cyclic-di-GMP homeostasis. Meanwhile, Orn is involved in the degradation of nanoRNAs, which can alter global gene expression by serving as transcription initiation primers. Previously, we found that Orn is required for the type III secretion system and pathogenesis ofP. aeruginosa, indicating a role of Orn in the bacterial response to environmental stimuli. Here we report that Orn is required for the tolerance ofP. aeruginosato ciprofloxacin. Transcriptome analysis of anornmutant revealed the upregulation of pyocin biosynthesis genes. Mutation of genes involved in pyocin biosynthesis in the background of anornmutant restored bacterial tolerance to ciprofloxacin. We further demonstrate that the upregulation of pyocin biosynthesis genes is due to RecA-mediated autoproteolysis of PrtR, which is the major negative regulator of pyocin biosynthesis genes. In addition, the SOS response genes were upregulated in theornmutant, indicating a DNA damage stress. Therefore, our results revealed a novel role of Orn in bacterial tolerance to ciprofloxacin.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Gukui
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore.|School of Biological Sciences, Division of Structural Biology and Biochemistry, Nanyang Technological University, Singapore, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore.|School of Biological Sciences, Division of Structural Biology and Biochemistry, Nanyang Technological University, Singapore, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China sjin@ufl.edu wuweihui@nankai.edu.cn.|Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China sjin@ufl.edu wuweihui@nankai.edu.cn.
authors.forename: Weihui
authors.initials: W
authors.lastname: Wu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology; D004361:Drug Tolerance / Q000235:genetics*; D005095:Exoribonucleases / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D011709:Pyocins / Q000096:biosynthesis*; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013014:SOS Response, Genetics; D059467:Transcriptome
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011709:Pyocins; D012097:Repressor Proteins; C079991:prtR protein, Pseudomonas aeruginosa; D002939:Ciprofloxacin; D011938:Rec A Recombinases; D005095:Exoribonucleases; C094587:oligoribonuclease
keywords: Pseudomonas aeruginosa; ciprofloxacin; oligoribonuclease; pyocin