Abstract
Helicobacter pylori is a highly pathogenic microorganism with various strategies to evade human immune responses. Nitric oxide (NO) and reactive nitrogen species (RNS) generated via nitric oxide synthase pathway are important effectors during the innate immune response. However, the mechanisms of H. pylori to survive the nitrosative stress are not clear. Here the proteomic approach has been used to define the adaptive response of H. pylori to nitrosative stress. Proteomic analysis showed that 38 protein spots were regulated by NO donor, sodium nitroprusside (SNP). These proteins were involved in protein processing, antioxidation, general stress response, and virulence, as well as some unknown functions. Particularly, some of them were participated in iron metabolism, potentially under the control of ferric uptake regulator (Fur). Real time PCR revealed that fur was induced under nitrosative stress, consistent with our deduction. One stress-related protein up-regulated under nitrosative conditions was thioredoxin reductase (TrxR). Inactivation of fur or trxR can lead to increased susceptivity to nitrosative stress respectively. These studies described the adaptive response of H. pylori to nitric oxide stress, and analyzed the relevant role of Fur regulon and TrxR in nitrosative stress management.
Citations
Citations to this article as recorded by

- Aminopeptidase M17 in bacteria: insights into structure, function, and potential as a drug target
Hussam Askar, Shengli Chen, Huafang Hao, Xiangrui Jin, Ahmed Adel Baz, Shimei Lan, Zhangcheng Li, Yuefeng Chu, Patricia A. Champion
Journal of Bacteriology.2026;[Epub] CrossRef - Detection and proteomic identification of in vivo S-nitrosylated proteins in Vibrio cholerae: A novel evidence
Shuddhasattwa Samaddar, Surupa Chakraborty, Rajib Sengupta, Sanjay Ghosh
Nitric Oxide.2025; 159: 63. CrossRef - From ubiquity to specificity: The diverse functions of bacterial thioredoxin systems
Cyril Anjou, Aurélie Lotoux, Claire Morvan, Isabelle Martin‐Verstraete
Environmental Microbiology.2024;[Epub] CrossRef - Bacterial Metalo-Aminopeptidases as Targets in Human Infectious
Diseases
Jorge González-Bacerio, Ana C. Varela, Mirtha E. Aguado, Maikel Izquierdo, Yanira Méndez, Maday A. del Rivero, Daniel G. Rivera
Current Drug Targets.2022; 23(12): 1155. CrossRef - Structural and Functional Basis of Potent Inhibition of Leishmanial Leucine Aminopeptidase by Peptidomimetics
Saleem Yousuf Bhat, Insaf Ahmed Qureshi
ACS Omega.2021; 6(29): 19076. CrossRef - Effects of active and latent H. pylori infection coupled with chronic alcohol ingestion on cytokine profiles and markers of oxidative balance in men seropositive for H. pylori CagA Ab
Yiguo Jia, Baoge Qu, Zhongdong Wang, Xinghai Han, Guangying Ren
Medicine.2018; 97(34): e11991. CrossRef - Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance
Melinda R. Grosser, Andy Weiss, Lindsey N. Shaw, Anthony R. Richardson, O. Schneewind
Journal of Bacteriology.2016; 198(15): 2043. CrossRef - Oxidative and nitrosative stress defences ofHelicobacterandCampylobacterspecies that counteract mammalian immunity
Annika Flint, Alain Stintzi, Lígia M. Saraiva, Michael Bott
FEMS Microbiology Reviews.2016; 40(6): 938. CrossRef - The Immune Battle against Helicobacter pylori Infection: NO Offense
Alain P. Gobert, Keith T. Wilson
Trends in Microbiology.2016; 24(5): 366. CrossRef - Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation
Stephanie L. Servetas, Beth M. Carpenter, Kathryn P. Haley, Jeremy J. Gilbreath, Jennifer A. Gaddy, D. Scott Merrell, T. J. Silhavy
Journal of Bacteriology.2016; 198(18): 2536. CrossRef - Helicobacter pyloriOuter Membrane Protein 18 (Hp1125) Is Involved in Persistent Colonization by Evading Interferon-γSignaling
Yuqun Shan, Xingxiao Lu, Yingnan Han, Xinpeng Li, Xiao Wang, Chunhong Shao, Lixiang Wang, Zhifang Liu, Wei Tang, Yundong Sun, Jihui Jia
BioMed Research International.2015; 2015: 1. CrossRef - Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis
Maroof Husain, Jessica Jones-Carson, Lin Liu, Miryoung Song, J. Royden Saah, Bryan Troxell, Mary Mendoza, Hosni Hassan, Andrés Vázquez-Torres, A. J. Bäumler
Infection and Immunity.2014; 82(1): 333. CrossRef - FrxA is an S‐nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity
Marta C. Justino, Margarida R. Parente, Ivo G. Boneca, Lígia M. Saraiva
The FEBS Journal.2014; 281(19): 4495. CrossRef - Random and site‐specific mutagenesis of the Helicobacter pylori ferric uptake regulator provides insight into Fur structure–function relationships
Jeremy J. Gilbreath, Oscar Q. Pich, Stéphane L. Benoit, Angelique N. Besold, Jeong‐Heon Cha, Robert J. Maier, Sarah L. J. Michel, Ernest L. Maynard, D. Scott Merrell
Molecular Microbiology.2013; 89(2): 304. CrossRef - Escherichia coli superoxide dismutase expression does not change in response to iron challenge during lag phase: Is the ferric uptake regulator to blame?
Robert L. Bertrand, Michael O. Eze
Advances in Enzyme Research.2013; 01(04): 132. CrossRef -
Fur Activates Expression of the 2-Oxoglutarate Oxidoreductase Genes (
oorDABC
) in Helicobacter pylori
Jeremy J. Gilbreath, Abby L. West, Oscar Q. Pich, Beth M. Carpenter, Sarah Michel, D. Scott Merrell
Journal of Bacteriology.2012; 194(23): 6490. CrossRef - Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator
R. Bertrand, D. Danielson, V. Gong, B. Olynik, M.O. Eze
Medical Hypotheses.2012; 78(1): 130. CrossRef - Non-Heme Iron Sensors of Reactive Oxygen and Nitrogen Species
Stephen Spiro, Benoît D'Autréaux
Antioxidants & Redox Signaling.2012; 17(9): 1264. CrossRef - Proteomic analysis of the function of spot in Helicobacter pylori anti‐oxidative stress in vitro and colonization in vivo
Yundong Sun, Xinpeng Li, Wen Li, Min Zhao, Lixiang Wang, Shili Liu, Jiping Zeng, Zhifang Liu, Jihui Jia
Journal of Cellular Biochemistry.2012; 113(11): 3393. CrossRef - Identification of S-nitrosylation of proteins of Helicobacter pylori in response to nitric oxide stress
Wei Qu, Yabin Zhou, Yundong Sun, Ming Fang, Han Yu, Wenjuan Li, Zhifang Liu, Jiping Zeng, Chunyan Chen, Chengjiang Gao, Jihui Jia
The Journal of Microbiology.2011; 49(2): 251. CrossRef - Respiratory nitrogen metabolism and nitrosative stress defence in ϵ-proteobacteria: the role of NssR-type transcription regulators
Melanie Kern, Christine Winkler, Jörg Simon
Biochemical Society Transactions.2011; 39(1): 299. CrossRef -
ygs
Is a Novel Gene That Influences Biofilm Formation and the General Stress Response of
Staphylococcus epidermidis
Xing Wang, Chen Niu, Gang Sun, Dandan Dong, Amer E. Villaruz, Min Li, Decheng Wang, Jianping Wang, Michael Otto, Qian Gao, A. Camilli
Infection and Immunity.2011; 79(3): 1007. CrossRef - The oxidative and nitrosative stress defence network of Wolinella succinogenes: cytochrome c nitrite reductase mediates the stress response to nitrite, nitric oxide, hydroxylamine and hydrogen peroxide
Melanie Kern, Jennifer Volz, Jörg Simon
Environmental Microbiology.2011; 13(9): 2478. CrossRef - Virulence factor cytotoxin-associated gene A in Helicobacter pylori is downregulated by interferon-γin vitro
Yinghui Zhao, Yabin Zhou, Yundong Sun, Ailian Yu, Han Yu, Wenjuan Li, Zhifang Liu, Jiping Zeng, Xi Li, Chunyan Chen, Jihui Jia
FEMS Immunology & Medical Microbiology.2011; 61(1): 76. CrossRef