title: HigB ofPseudomonas aeruginosaEnhances Killing of Phagocytes by Up-Regulating the Type III Secretion System in Ciprofloxacin Induced Persister Cells.
abstract: Bacterial persister cells are dormant and highly tolerant to lethal antibiotics, which are believed to be the major cause of recurring and chronic infections. Activation of toxins of bacterial toxin-antitoxin systems inhibits bacterial growth and plays an important role in persister formation. However, little is known about the overall gene expression profile upon toxin activation. More importantly, how the dormant bacterial persisters evade host immune clearance remains poorly understood. Here we demonstrate that aPseudomonas aeruginosatoxin-antitoxin system HigB-HigA is required for the ciprofloxacin induced persister formation. Transcriptome analysis of ahigA::Tn mutant revealed up regulation of type III secretion systems (T3SS) genes. Overexpression of HigB increased the expression of T3SS genes as well as bacterial cytotoxicity. We further demonstrate that wild type bacteria that survived ciprofloxacin treatment contain higher levels of T3SS proteins and display increased cytotoxicity to macrophage compared to vegetative bacterial cells. These results suggest thatP. aeruginosaaccumulates T3SS proteins during persister formation, which can protect the persister cells from host clearance by efficiently killing host immune cells.
authors: 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: Mei
authors: M
authors: Li
authors: 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: Yuqing
authors: Y
authors: Long
authors: 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: Ying
authors: Y
authors: Liu
authors: Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University Singapore, Singapore.
authors: Yang
authors: Y
authors: Liu
authors: 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: Ronghao
authors: R
authors: Chen
authors: 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: Jing
authors: J
authors: Shi
authors: 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: Lu
authors: L
authors: Zhang
authors: 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: Yongxin
authors: Y
authors: Jin
authors: Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological UniversitySingapore, Singapore; School of Biological Sciences, Division of Structural Biology and Biochemistry, Nanyang Technological UniversitySingapore, Singapore.
authors: Liang
authors: L
authors: Yang
authors: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy and Life Sciences, Nankai University Tianjin, China.
authors: Fang
authors: F
authors: Bai
authors: 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 UniversityTianjin, China; Department of Molecular Genetics and Microbiology, College of Medicine, University of FloridaGainesville, FL, USA.
authors: Shouguang
authors: S
authors: Jin
authors: 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: Zhihui
authors: Z
authors: Cheng
authors: 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: Weihui
authors: W
authors: Wu
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002470:Cell Survival; D002939:Ciprofloxacin / Q000378:metabolism*; D004251:DNA Transposable Elements; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D016254:Mutagenesis, Insertional; D010586:Phagocytes / Q000382:microbiology / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000069296:Type III Secretion Systems / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004251:DNA Transposable Elements; D000069296:Type III Secretion Systems; D002939:Ciprofloxacin
keywords: Pseudomonas aeruginosa; gene regulation; persistence; toxin/antitoxin; type III secretion system