title: The CrdRS two-component system in Helicobacter pylori responds to nitrosative stress.
abstract: Helicobacter pylori inhabits the gastric mucosa where it senses and responds to various stresses via a two-component systems (TCSs) that enable its persistent colonization. The aim of this study was to investigate whether any of the three paired TCSs (ArsRS, FleRS and CrdRS) in H. pylori respond to nitrosative stress. The results showed that the expression of crdS was significantly increased upon exposure to nitric oxide (NO). crdS-knockout (ΔcrdS) and crdR/crdS-knockout (ΔcrdRS) H. pylori, but not arsS-knockout (ΔarsS) or fleS-knockout (ΔfleS) H. pylori, showed a significant loss of viability upon exposure to NO compared with wild-type strain. Knockin crdS (ΔcrdS-in) significantly restored viability in the presence of NO. Global transcriptional profiling analysis of wild-type and ΔcrdS H. pylori in the presence or absence of NO showed that 101 genes were differentially expressed, including copper resistance determinant A (crdA), transport, binding and envelope proteins. The CrdR binding motifs were investigated by competitive electrophoretic mobility shift assay, which revealed that the two AC-rich regions in the crdA promoter region are required for binding. These results demonstrate that CrdR-crdA interaction enables H. pylori to survive under nitrosative stress.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, California, USA.|Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chiu-Lien
authors.initials: CL
authors.lastname: Hung
authors.affiliation: Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Cheng
authors.affiliation: Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan.
authors.forename: Zing Tsung-Yeh
authors.initials: ZT
authors.lastname: Tsai
authors.affiliation: Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan.
authors.forename: Huai-Kuang
authors.initials: HK
authors.lastname: Tsai
authors.affiliation: Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Han
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Hsieh
authors.affiliation: Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsou
authors.affiliation: Department of Nursing, Asia University, Taichung, Taiwan.|Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan.|Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.|Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Wang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D003300:Copper / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D009569:Nitric Oxide; D003300:Copper