- Helicobacter pylori-mediated gastric pathogenesis is attenuated by treatment of 2-deoxyglucose and metformin
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Hanfu Su , Eun-Jung Bak , Aeryun Kim , Kavinda Tissera , Jeong-Heon Cha , Sungil Jang
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J. Microbiol. 2022;60(8):849-858. Published online June 22, 2022
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DOI: https://doi.org/10.1007/s12275-022-2130-z
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1,081
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Helicobacter pylori infection causes chronic inflammation
in the stomach, which is linked to the development of gastric
cancer. The anti-inflammatory and anticancer effects of a
glycolysis inhibitor 2-deoxyglucose (2DG) and an antidiabetic
medication metformin (Met) have gotten attention. Using a
Mongolian gerbil animal model, we investigated H. pylorimediated
gastric pathogenesis and how this pathogenesis is
influenced by 2DG and Met. Five-week-old male gerbils were
infected with H. pylori strain 7.13. After 2 weeks of infection,
gerbils were fed 2DG-containing food (0.03% w/w), Met-containing
water (0.5% w/v), or both (Combi) for 2 (short-term)
or 10 weeks (long-term). Gastric pathogenesis and host response
to H. pylori infection were examined by macroscopic
and histopathologic analysis of gerbils’ stomach. As a result,
indicators of gastric pathogenesis by H. pylori infection including
infiltration of polymorphonuclear neutrophils and
lymphocytes, intestinal metaplasia, atrophy, and proliferation
of gastric epithelial cells were attenuated by short-term administration
of 2DG, Met, or Combi. When the infection was
sustained for long-term, gastric pathogenesis in drug-treated
gerbils was equivalent to that in untreated gerbils, with the
exception that the infiltration of neutrophil was reduced by
2DG. Colonization of H. pylori in stomach was unaffected
by both short- and long-term treatments. Our findings demonstrate
that the progression of gastric pathogenesis induced
by H. pylori infection can be attenuated by the shortterm
individual or combinational treatment of 2DG and
Met, implying that 2DG or Met could be considered as a
treatment option for gastric diseases in the early stages of
infection.
-
Citations
Citations to this article as recorded by 
- Metabolic reprogramming as a key regulator in Helicobacter pylori-infected gastric cancer
Ruofan Cao, Feifei Zhou, Cuiyu Zhu, Hongwei Xu Gastric Cancer.2026; 29(1): 1. CrossRef - Chemoprevention strategies for precancerous gastric lesions beyond Helicobacter pylori eradication
Tai Zhang, Xudong Tang QJM: An International Journal of Medicine.2025; 118(6): 385. CrossRef - Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model
Hassan Valadbeigi, Saeed Khoshnood, Babak Negahdari, Mohd Azmuddin Abdullah, Mohammad Hossein Haddadi, Abhimanyu Abhimanyu BioMed Research International.2023;[Epub] CrossRef - Effect of Metformin on the Prognosis of Gastric Cancer Patients with Type 2 Diabetes Mellitus: A Meta-Analysis Based on Retrospective Cohort Studies
Lingna Li, Jianing Huang, Tongmin Huang, Jie Yao, Yeyuan Zhang, Meiling Chen, Haojie Shentu, Haiying Lou, Flavia Prodam International Journal of Endocrinology.2023; 2023: 1. CrossRef
- Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
-
Kavinda Tissera , Myeong-A Kim , Jing Lai , Sacheera Angulmaduwa , Aeryun Kim , D. Scott Merrell , Ji-Hye Kim , Hanfu Su , Jeong-Heon Cha
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J. Microbiol. 2022;60(2):207-214. Published online November 10, 2021
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DOI: https://doi.org/10.1007/s12275-022-1483-7
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1,076
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3
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4
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Abstract
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The polymorphic bacterial oncoprotein, CagA shows geography-
dependent variation in the C-terminal Glu-Pro-Ile-
Tyr-Ala (EPIYA) motifs; East-Asian H. pylori isolates carry
the ABD type while Western isolates carry the ABC type. In
Western isolates, the EPIYA-C motif is sometimes found in
multi-copy and this genotype is associated with disease severity.
Interestingly, a small number of East-Asian H. pylori
isolates have been found to carry Western ABC-type CagA.
To gain a better understanding of these unusual isolates, the
genomes of four Korean H. pylori clinical isolates carrying
ABC-type CagA were sequenced via third generation (Pac-
Bio SMRT) sequencing technology. The obtained data were
utilized for phylogenetic analysis as well as comparison of
additional virulence factors that are known to show geographic-
dependent polymorphisms. Three of four isolates indeed
belonged to the hpEastAsia group and showed typical East-
Asian polymorphism in virulence factors such as homA/B/C,
babA/B/C, and oipA. One isolate grouped to HpAfrica and
showed typical Western polymorphism of virulence factors
such as cagA, homA/B/C, and oipA. To understand the occurrence
of the multi-copy EPIYA-C motif genotype in an East-
Asian H. pylori background, the Korean clinical isolate, K154
was analyzed; this strain belonged to hpEastAsia but encoded
CagA EPIYA-ABCCCC. Based on DNA sequence homology
within the CagA multimerization (CM) sequence that flanked
the EPIYA-C motifs, we predicted that the number of C motifs
might change via homologous recombination. To test this
hypothesis, K154 was cultured for one generation and 287
single colonies were analyzed for the number of EPIYA-C
motifs using PCR-based screening and DNA sequencing verification.
Three out of 284 (1%) single colony isolates showed
changes in the number of EPIYA-C motifs in vitro; one isolate
increased to five EPIYA-C motifs, one decreased to three
EPIYA-C motifs, and one completely deleted the EPIYA-C
motifs. The capacity for dynamic changes in the number of
EPIYA-C repeats of CagA may play a role in generating important
intraspecies diversity in East-Asian H. pylori.
-
Citations
Citations to this article as recorded by 
- Helicobacter pylori’s Seven-housekeeping Gene and CagA EPIYA Motif Patterns Linking to Gastrointestinal Diseases
Nattamon Narkwichearn, Phataraporn Khumphai, Sasiporn Tongman, K.-S. Cheng BIO Web of Conferences.2025; 163: 01002. CrossRef - Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer
Zhijing Xue, Weijia Li, Hailing Ding, Fengyan Pei, Jianzhong Zhang, Yanan Gong, Ruyue Fan, Fang Wang, Youjun Wang, Qing Chen, Yanran Li, Xinyu Yang, Yan Zheng, Guohai Su, Saeid Ghavami PLOS ONE.2024; 19(9): e0309844. CrossRef - Amino acid deletions at positions 893 and 894 of cytotoxin-associated gene A protein affect Helicobacter pylori gastric epithelial cell interactions
Zhi-Jing Xue, Ya-Nan Gong, Li-Hua He, Lu Sun, Yuan-Hai You, Dong-Jie Fan, Mao-Jun Zhang, Xiao-Mei Yan, Jian-Zhong Zhang World Journal of Gastroenterology.2024; 30(41): 4449. CrossRef - Characteristics of different types of Helicobacter pylori: New evidence from non-amplified white light endoscopy
Weidong Liu, Wenjie Kong, Wenjia Hui, Chun Wang, Qi Jiang, Hong Shi, Feng Gao Frontiers in Microbiology.2023;[Epub] CrossRef
- Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates
-
Aeryun Kim , Jing Lai , D. Scott Merrell , Ji-Hye Kim , Hanfu Su , Jeong-Heon Cha
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J. Microbiol. 2021;59(12):1125-1132. Published online October 31, 2021
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DOI: https://doi.org/10.1007/s12275-021-1450-8
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989
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5
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4
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Abstract
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Helicobacter pylori outer membrane inflammatory protein
A (OipA) was originally named for its role in inducing inflammation
in the host, as evidenced by high mucosal IL-8
levels. Expression of OipA is regulated by phase variation of
a CT dinucleotide-repeat located in the 5region of the gene.
However, little is known about OipA geographic diversity
across isolates. To address this gap, we conducted a large-scale
molecular epidemiologic analysis using H. pylori clinical isolates
obtained from two geographically distinct populations:
Korea and the United States (US). Most Korean isolates (98.7%)
possessed two copies of oipA located at two specific loci (A
and B) while all US isolates contained only one copy of oipA
at locus A. Furthermore, most Korean oipA (94.8%) possessed
three or less CT repeats while most US oipA (96.6%) contained
five or more CT repeats. Among the two copies, all Korean
H. pylori possessed at least one oipA ‘on’ phase variant while
the single copy of oipA in US isolates showed 56.2% ‘on’ and
43.8% ‘off.’ Thus, host differences seem to have driven geographic
diversification of H. pylori across these populations
such that OipA expression in US isolates is still regulated by
phase variation with 5 or more CT repeats, while Korean isolates
always express OipA; duplication of the oipA combined
with a reduction of CT repeats to three or less ensures continued
expression. En masse, these findings suggest that diversity
in the oipA gene copy number, CT repeats, and phase
variation among H. pylori from different populations may
confer a benefit in adaptation to particular host populations.
-
Citations
Citations to this article as recorded by 
-
Helicobacter pylori
geographic variation: a window into global differences in gastric cancer incidence
Chiamaka D. Okoye, Georgia C. Caso, Timothy L. Cover, Federico Rey Microbiology and Molecular Biology Reviews.2026;[Epub] CrossRef -
Pathogenicity and virulence of
Helicobacter pylori
: A paradigm of chronic infection
Marguerite Clyne, Tadhg Ó Cróinín Virulence.2025;[Epub] CrossRef - Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam
Thi Hong Nhung Thai, Hong Phong Nguyen, Thi Hai Yen Nguyen, Thi Be Hai Nguyen, Thai Hoa Nguyen, Thi Mai Ngan Nguyen, Thi Minh Thi Ha Infection, Genetics and Evolution.2023; 112: 105438. CrossRef - Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
Kavinda Tissera, Myeong-A Kim, Jing Lai, Sacheera Angulmaduwa, Aeryun Kim, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha Journal of Microbiology.2022; 60(2): 207. CrossRef
- CagL polymorphisms between East Asian and Western Helicobacter pylori are associated with different abilities to induce IL-8 secretion
-
Yun Hui Choi , Jing Lai , Myeong-A Kim , Aeryun Kim , Jinmoon Kim , Hanfu Su , Linhu Ge , Jeong-Heon Cha
-
J. Microbiol. 2021;59(8):763-770. Published online June 1, 2021
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DOI: https://doi.org/10.1007/s12275-021-1136-2
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999
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7
Web of Science
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5
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Abstract
PDF
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Helicobacter pylori colonizes human gastric mucosa. Its infection
is associated with gastric diseases including gastric
cancer. CagA is one of the most important toxins produced
by H. pylori. It is related to gastric cancer which can be injected
into host cells via a type IV secretion system (T4SS).
CagL is a structural component of T4SS apparatus, which
triggers host cell signaling pathway. It has been reported that
CagL polymorphisms may influence the severity of disease
development. To explore the contribution of CagL polymorphisms
between East Asian and Western H. pylori in pathogenesis,
cagL gene in G27 H. pylori was swapped by K74 cagL
which is identical to East Asian CagL consensus sequence and
by Western 26695 H. pylori, resulting in G27ΔcagL/cagLK74
and G27ΔcagL/cagL26695, respectively. Intriguingly, G27ΔcagL/
cagLK74 showed significantly less ability of IL-8 induction
than G27ΔcagL/cagL26695 while displayed similar abilities of
CagA phosphorylation, and cell elongation. Taken together,
this study suggests that the CagL polymorphism may influence
IL-8 induction, and K74 CagL has less ability to induce
IL-8 secretion than G27 or 26695 CagL. Further research
should address how the different capabilities of IL-8 induction
between intraspecies-CagL are associated with the large
differences of the incidence of gastric cancer between East
Asian and Western countries.
-
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- Integrative bioinformatics and machine learning identify shared molecular mechanisms and diagnostic biomarkers between Helicobacter pylori infection and atrial fibrillation
Aojian Deng, Wei Wang, Tomasz W. Kaminski PLOS One.2026; 21(4): e0346038. CrossRef -
Roles of the components of the
cag
-pathogenicity island encoded type IV secretion system in
Helicobacter pylori
Lingzhu Gou, Xiaoping Yang, Jianwei Yun, Zenghui Ma, Xiaofeng Zheng, Hongwei Du, Dekui Zhang Future Microbiology.2024; 19(14): 1253. CrossRef - Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model
Hassan Valadbeigi, Saeed Khoshnood, Babak Negahdari, Mohd Azmuddin Abdullah, Mohammad Hossein Haddadi, Abhimanyu Abhimanyu BioMed Research International.2023;[Epub] CrossRef - New CagL Amino Acid Polymorphism Patterns of Helicobacter pylori in Peptic Ulcer and Non-Ulcer Dyspepsia
Reyhan Caliskan, Silva Polat Sari, Bahadir Ercan, Kivanc Derya Peker, Mehtap Omac Sonmez, Ozer Akgul, Burcu Sapmaz, Aliye Soylu, Gokhan Tolga Adas, Yasar Ali Oner, Pelin Yuksel Mayda Medicina.2022; 58(12): 1738. CrossRef - Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates
Aeryun Kim, Jing Lai, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha Journal of Microbiology.2021; 59(12): 1125. CrossRef
- N-acetylcysteine prevents the development of gastritis induced by Helicobacter pylori infection
-
Sungil Jang , Eun-Jung Bak , Jeong-Heon Cha
-
J. Microbiol. 2017;55(5):396-402. Published online April 29, 2017
-
DOI: https://doi.org/10.1007/s12275-017-7089-9
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3,896
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7
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14
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Abstract
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Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various gastric diseases ranging from gastritis to gas-tric adenocarcinoma. It has been reported that combining N-acetylcysteine (NAC) with conventional antibiotic therapy increases the success rate of H. pylori eradication. We evalu-ated the effect of NAC itself on the growth and coloniza-tion of H. pylori, and development of gastritis, using in vitro liquid culture system and in vivo animal models. H. pylori growth was evaluated in broth culture containing NAC. The H. pylori load and histopathological scores of stomachs were measured in Mongolian gerbils infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid culture, NAC inhibited H. pylori growth in a concentration-depen-dent manner. In the animal model, 3-day administration of NAC after 1 week from infection reduced the H. pylori load; 6-week administration of NAC after 1 week from infection prevented the development of gastritis and reduced H. pylori colonization. However, no reduction in the bacterial load or degree of gastritis was observed with a 6-week administ-ration of NAC following 6-week infection period. Our results indicate that NAC may exert a beneficial effect on reduction of bacterial colonization, and prevents the development of severe inflammation, in people with initial asymptomatic or mild H. pylori infection.
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Kang Li, Shiqi Tang, Jingfeng Ding, Yuqing Yang, Haokai Chen, Qiqi Jiang, Xiumei Wei, Jialong Yang Aquaculture.2026; 620: 743949. CrossRef - Role of N-acetylcysteine and vitamin B complex in improving outcomes of corrosive ingestion
Heidi El-Sobky, Safaa Mostafa El-Shanawany, Maha Ghanem, Maram Atef Toxicology Research.2024;[Epub] CrossRef - Helicobacter pylori: Routes of Infection, Antimicrobial Resistance, and Alternative Therapies as a Means to Develop Infection Control
Ayman Elbehiry, Adil Abalkhail, Nuha Anajirih, Fahad Alkhamisi, Mohammed Aldamegh, Abdullah Alramzi, Riyad AlShaqi, Naif Alotaibi, Abdullah Aljuaid, Hilal Alzahrani, Feras Alzaben, Mohammed Rawway, Mai Ibrahem, Moustafa H. Abdelsalam, Nermin I. Rizk, Moha Diseases.2024; 12(12): 311. CrossRef - Isotope tracing reveals bacterial catabolism of host-derived glutathione during Helicobacter pylori infection
Maia J. Baskerville, Yekaterina Kovalyova, Raquel Mejías-Luque, Markus Gerhard, Stavroula K. Hatzios, William Navarre PLOS Pathogens.2023; 19(7): e1011526. CrossRef - Helicobacter pylori-mediated gastric pathogenesis is attenuated by treatment of 2-deoxyglucose and metformin
Hanfu Su, Eun-Jung Bak, Aeryun Kim, Kavinda Tissera, Jeong-Heon Cha, Sungil Jang Journal of Microbiology.2022; 60(8): 849. CrossRef - Population Pharmacokinetics of Doxycycline, Administered Alone or with N-Acetylcysteine, in Chickens with Experimental Mycoplasma gallisepticum Infection
Tsvetelina Petkova, Antoaneta Yordanova, Aneliya Milanova Pharmaceutics.2022; 14(11): 2440. CrossRef - N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)
Gerry K. Schwalfenberg, Tatiana Emanuelli Journal of Nutrition and Metabolism.2021; 2021: 1. CrossRef - Enhanced Eradication of Mucin‐Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers
Stine Egebro Birk, Laura Serioli, Valentina Cavallo, Janus Anders Juul Haagensen, Søren Molin, Line Hagner Nielsen, Kinga Zór, Anja Boisen Macromolecular Bioscience.2021;[Epub] CrossRef - N-Acetylcysteine (NAC): Impacts on Human Health
Micaely Cristina dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira, Marília Oliveira Fonseca Goulart Antioxidants.2021; 10(6): 967. CrossRef -
N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli
Ana I Rodríguez-Rosado, Estela Ynés Valencia, Alexandro Rodríguez-Rojas, Coloma Costas, Rodrigo S Galhardo, Jerónimo Rodríguez-Beltrán, Jesús Blázquez Journal of Antimicrobial Chemotherapy.2019; 74(8): 2188. CrossRef - N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs
Jing Cui, Li Tang, Quan Hong, Shupeng Lin, Xuefeng Sun, Guangyan Cai, Xue-Yuan Bai, Xiangmei Chen Shock.2019; 52(6): 622. CrossRef - Allantoin improves histopathological evaluations in a rat model of gastritis
M Eslami-farsani, A Moslehi, A Hatami-shahmir Physiology International.2018; 105(4): 325. CrossRef - N‐Acetylcysteine Reduces ROS‐Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection
Chuan Xie, Jian Yi, Jing Lu, Muwen Nie, Meifang Huang, Jianfang Rong, Zhenhua Zhu, Jiang Chen, Xiaoliang Zhou, Bimin Li, Haiming Chen, Nonghua Lu, Xu Shu, Rômulo D. Novaes Oxidative Medicine and Cellular Longevity.2018;[Epub] CrossRef - Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils
Le Guo, Hua Yang, Feng Tang, Runting Yin, Hongpeng Liu, Xiaojuan Gong, Jun Wei, Ying Zhang, Guangxian Xu, Kunmei Liu Frontiers in Cellular and Infection Microbiology.2017;[Epub] CrossRef
- Cot kinase plays a critical role in Helicobacter pylori-induced IL-8 expression
-
Sungil Jang , Jinmoon Kim , Jeong-Heon Cha
-
J. Microbiol. 2017;55(4):311-317. Published online March 31, 2017
-
DOI: https://doi.org/10.1007/s12275-017-7052-9
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949
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0
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4
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Abstract
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-
Helicobacter pylori is a major pathogen causing various gastric
diseases including gastric cancer. Infection of H. pylori
induces pro-inflammatory cytokine IL-8 expression in gastric
epithelial cells in the initial inflammatory process. It has been
known that H. pylori can modulate Ras-Raf-Mek-Erk signal
pathway for IL-8 induction. Recently, it has been shown that
another signal molecule, cancer Osaka thyroid oncogene/tumor
progression locus 2 (Cot/Tpl2) kinase, activates Mek and
Erk and plays a role in the Erk pathway, similar to MAP3K
signal molecule Raf kinase. Therefore, the objective of this
study was to determine whether Cot kinase might be involved
in IL-8 induction caused by H. pylori infection. AGS gastric
epithelial cells were infected by H. pylori strain G27 or its isogenic
mutants lacking cagA or type IV secretion system followed
by treatment with Cot kinase inhibitor (KI) or siRNA
specific for Cot kinase. Activation of Erk was assessed by
Western blot analysis and expression of IL-8 was measured
by ELISA. Treatment with Cot KI reduced both transient and
sustained Erk activation. It also reduced early and late IL-8
secretion in the gastric epithelial cell line. Furthermore, siRNA
knockdown of Cot inhibited early and late IL-8 secretion
induced by H. pylori infection. Taken together, these results
suggest that Cot kinase might play a critical role in H. pylori
type IV secretion apparatus-dependent early IL-8 secretion
and CagA-dependent late IL-8 secretion as an alternative
signaling molecule in the Erk pathway.
-
Citations
Citations to this article as recorded by 
- Helicobacter pylori infection is correlated with the incidence of erosive oral lichen planus and the alteration of the oral microbiome composition
Shutong Li, Yangheng Zhang, Zongcheng Yang, Jingyuan Li, Ya Li, Huanjie Li, Wenjuan Li, Jihui Jia, Shaohua Ge, Yundong Sun BMC Microbiology.2021;[Epub] CrossRef - Foot-and-Mouth Disease Virus Structural Protein VP1 Destroys the Stability of the TPL2 Trimer by Degradation of TPL2 To Evade Host Antiviral Immunity
Keshan Zhang, Minghao Yan, Junhong Hao, Chaochao Shen, Zixiang Zhu, Dajun Zhang, Jing Hou, Guowei Xu, Dan Li, Haixue Zheng, Xiangtao Liu, Susana López Journal of Virology.2021;[Epub] CrossRef - Discovery and validation of methylated-differentially expressed genes in Helicobacter pylori-induced gastric cancer
Duanrui Liu, Xiaoli Ma, Fei Yang, Dongjie Xiao, Yanfei Jia, Yunshan Wang Cancer Gene Therapy.2020; 27(6): 473. CrossRef - Probiotic effect on Helicobacter�pylori attachment and inhibition of inflammation in human gastric epithelial cells
Hanyi Song, Long Zhou, Dongyan Liu, Lihui Ge, Yan Li Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
- Helicobacter pylori outer membrane protein, HomC, shows geographic dependent polymorphism that is influenced by the Bab family
-
Aeryun Kim , Stephanie L. Servetas , Jieun Kang , Jinmoon Kim , Sungil Jang , Yun Hui Choi , Hanfu Su , Yeong-Eui Jeon , Youngmin A. Hong , Yun-Jung Yoo , D. Scott Merrell , Jeong-Heon Cha
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J. Microbiol. 2016;54(12):846-852. Published online November 26, 2016
-
DOI: https://doi.org/10.1007/s12275-016-6434-8
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1,010
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The array of outer membrane proteins (OMPs) found in
Helicobacter pylori provides a crucial component for persistent
colonization within the gastric niche. Not only does
H. pylori harbor a wide number of OMPs, but these OMPs
often vary across strains; this likely contributes to immune
evasion, adaptation during long term colonization, and potentially
differential disease progression. Previous work from
our group described OMP differences among the Bab family
(babA, babB, and babC) and Hom family (homA and homB)
from 80 American H. pylori clinical isolates (AH) and 80
South Korean H. pylori clinical isolates (KH). In the current
study, we expanded our investigation to include the less well
characterized Hom family member, HomC.
Overall, we identified and genotyped three homC variants:
homCS, homCL, and homCM, in both populations. Similar to
other polymorphic genes, the KH group showed less overall
diversity, with 97.5% of strains harboring homCL. In contrast,
a more heterogeneous profile was observed in strains
derived from an American population; we found nearly equal
distribution of homCS and homCL. Further analysis of the AH
group identified associations between homC polymorphism
and bab genotype; in AH strains, there was a significant association
between homCL and carriage of babA at locus A.
Since babA is an important virulence factor for the development
of severe gastric disease, these data may suggest that
homC polymorphism plays a role in H. pylori pathogenesis.
-
Citations
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A unique
Helicobacter pylori
strain to study gastric cancer development
Jeannette M. Whitmire, Ian H. Windham, Morris O. Makobongo, Mandy D. Westland, Sirena C. Tran, Jaume Piñol, Yvonne Hui, Rasha Raheem Alkarkoushi, Oscar Q. Pich, David J. McGee, M. Blanca Piazuelo, Angela Melton-Celsa, Traci L. Testerman, Timothy L. Cover, Microbiology Spectrum.2025;[Epub] CrossRef - Helicobacter pylori outer membrane protein families and related pathogenesis
Senlin You, Jiao Li, Eng Guan Chua, Alfred Tay, Mohammed Benghezal, Barry Marshall, Hong Tang, Hong Li Microbial Pathogenesis.2025; 206: 107740. CrossRef - Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity
Arghyadeep Bhattacharjee, Om Saswat Sahoo, Ahana Sarkar, Saurabh Bhattacharya, Rukhsana Chowdhury, Samarjit Kar, Oindrilla Mukherjee Infection.2024; 52(2): 345. CrossRef - (Re)-definition of the holo- and apo-Fur direct regulons of Helicobacter pylori
Andrea Vannini, Eva Pinatel, Paolo Emidio Costantini, Simone Pelliciari, Davide Roncarati, Simone Puccio, Gianluca De Bellis, Vincenzo Scarlato, Clelia Peano, Alberto Danielli Journal of Molecular Biology.2024; 436(10): 168573. CrossRef - Biofilm of Helicobacter pylori: Life Cycle, Features, and Treatment Options
Yasmine Elshenawi, Shuai Hu, Skander Hathroubi Antibiotics.2023; 12(8): 1260. CrossRef -
Recent Progress in Biomarker-Based Diagnostics of
Helicobacter pylori
, Gastric Cancer-Causing Bacteria
Kirti Saxena, Akanksha Deshwal, Ramesh Namdeo Pudake, Utkarsh Jain, Ravi Mani Tripathi Biomarkers in Medicine.2023; 17(16): 679. CrossRef -
Genomic diversity of
Helicobacter pylori
populations from different regions of the human stomach
Daniel James Wilkinson, Benjamin Dickins, Karen Robinson, Jody Anne Winter Gut Microbes.2022;[Epub] CrossRef - Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates
Aeryun Kim, Jing Lai, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha Journal of Microbiology.2021; 59(12): 1125. CrossRef - Virulence of Helicobacter pylori outer membrane proteins: an updated review
Chenjing Xu, Djaleel Muhammad Soyfoo, Yao Wu, Shunfu Xu European Journal of Clinical Microbiology & Infectious Diseases.2020; 39(10): 1821. CrossRef - Comparative analysis of the Hom family of outer membrane proteins in isolates from two geographically distinct regions: The United States and South Korea
Stephanie L. Servetas, Aeryun Kim, Hanfu Su, Jeong‐Heon Cha, D. Scott Merrell Helicobacter.2018;[Epub] CrossRef
- Role of bacterial γ-glutamyltranspeptidase as a novel virulence factor in bone-resorbing pathogenesis
-
Jinmoon Kim , Sungil Jang , Aeryun Kim , Hanfu Su , Niluka Gunawardhana , Yeong-Eui Jeon , Eun Jung Bak , Ji-Hye Kim , Jeong-Heon Cha
-
J. Microbiol. 2016;54(5):396-402. Published online April 20, 2016
-
DOI: https://doi.org/10.1007/s12275-016-6137-1
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914
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Mammalian γ-glutamyltranspeptidase (GGT) has been identified
as a bone-resorbing factor. Since GGT of Bacillus subtilis
exhibits similarity in their primary structure and enzymatic
characteristics with mammalian GGTs, the bone-resorbing
activity of bacterial GGT was examined in this study. Osteoclastogenesis
was performed in a co-culture system of mouse
calvaria-derived osteoblasts and bone marrow cells. A conditioned
medium from GGT-overproducing B. subtilis culture
showed significantly higher activity of osteoclast formation
than a conditioned medium from wild-type B. subtilis culture.
Recombinant GGT (rGGT) of wild-type B. subtilis and an
enzymatic activity-defected rGGT of B. subtilis 2288 mutant
were expressed in Escherichia coli and purified using His tag.
Both purified rGGTs induced similar levels of osteoclastogenesis,
suggesting that B. subtilis GGT possesses virulent boneresorbing
activity and its activity is probably independent of
its enzymatic activity. Furthermore, a recombinant protein of
B. subtilis GGT heavy subunit (Bs rGGT/H) showed strong
activity of osteoclastogenesis while the light subunit failed to
show strong activity, suggesting that the bone-resorbing activity
is mainly located at the heavy subunit. More importantly,
the GGT enzymatic activity may not be required for this virulence
activity since the light subunit contains the catalytic
pocket. In addition, B. subtilis rGGT stimulated mRNA expressions
of receptor activator of nuclear factor kappa-B ligand
(RANKL) and cyclooxygenase-2 (COX-2), while an
osteoprotegerin inhibited the osteoclast formation induced by Bs rGGT/H. This is the first demonstration that bacterial
GGT itself is sufficient to act as a bone-resorbing virulence
factor via RANKL-dependent pathway. Therefore, it can be
hypothesized that GGT of periodontopathic bacteria may play
an important role as a virulence factor in bone destruction.
-
Citations
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- Complementation System for Helicobacter pylori
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Jinmoon Kim , Sung-Whan Kim , Sungil Jang , D. Scott Merrell , Jeong-Heon Cha
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J. Microbiol. 2011;49(3):481-486. Published online June 30, 2011
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DOI: https://doi.org/10.1007/s12275-011-1196-9
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Previously Langford et al. (2006) developed the pIR203C04 complementation system for Helicobacter pylori, which can be used to complement and restore phenotypic effects in H. pylori mutant, and furthermore they used the complementation system in vivo experiments to animals without altering the ability of strain SS1 to colonize mice. In their previous study, the pIR203C04 was able to transform 26695, SS1, J99, and 43504 H. pylori strains by an electroporation method. However, in the present study using a natural transformation the pIR203C04 transformed only 26695 H. pylori but not SS1, J99, 7.13, and G27 H. pylori strains. Since the useful complementation system has a limitation of narrow selection among H. pylori strains, we redesigned the complementation system for the improvement. The same intergenic chromosomal site between hp0203 and hp0204 was utilized for the new complementation system because the insertion at the intergenic site didn’t show any polar effects and disruption of other H. pylori genes. The genome sequence analysis showed that the intergenic regions among H. pylori strains may have too low homology to each others to do a homologous recombination. Thus, in addition to the short intergenic region, the fragments of the new complementation system included 3′ conserved parts of hp0203 and hp0204 coding regions. Between the fragments there are a chloramphenicol acetyltransferase cassette and multicloning sites, resulting in pKJMSH. DNA fragment of the interest can be cloned into the multicloning sites of pKJMSH and the fragment can be integrated at the intergenic region of H. pylori chromosome by the homologous recombination. Indeed, by the natural transformation, pKJMSH was able to transform all five H. pylori strains of 26695, SS1, J99, 7.13, and G27, which are common for the investigation of molecular pathogenesis. Thus, the new pKJMSH complementation system is applicable to most H. pylori wild-type stains.
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Huang Yang, Xiaoxing Huang, Xiaochuan Zhang, Xiaoyan Zhang, Xiaohong Xu, Feifei She, Yancheng Wen Frontiers in Medicine.2022;[Epub] CrossRef - Dynamic Expansion and Contraction ofcagACopy Number inHelicobacter pyloriImpact Development of Gastric Disease
Sungil Jang, Hanfu Su, Faith C. Blum, Sarang Bae, Yun Hui Choi, Aeryun Kim, Youngmin A. Hong, Jinmoon Kim, Ji-Hye Kim, Niluka Gunawardhana, Yeong-Eui Jeon, Yun-Jung Yoo, D. Scott Merrell, Linhu Ge, Jeong-Heon Cha, Martin J. Blaser mBio.2017;[Epub] CrossRef - Helicobacter pylori outer membrane protein, HomC, shows geographic dependent polymorphism that is influenced by the Bab family
Aeryun Kim, Stephanie L. Servetas, Jieun Kang, Jinmoon Kim, Sungil Jang, Yun Hui Choi, Hanfu Su, Yeong-Eui Jeon, Youngmin A. Hong, Yun-Jung Yoo, D. Scott Merrell, Jeong-Heon Cha Journal of Microbiology.2016; 54(12): 846. CrossRef
- Mouse Strain-Dependent Osteoclastogenesis in Response to Lipopolysaccharide
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Ho Gil Choi , Jin Moon Kim , Bong-Ju Kim , Yun-Jung Yoo , Jeong-Heon Cha
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J. Microbiol. 2007;45(6):566-571.
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DOI: https://doi.org/2607 [pii]
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Abstract
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Bacterial lipopolysaccharide (LPS) is a potent stimulator of bone resorption in periodontitis. Co-culture systems of mouse calvaria-derived osteoblasts and bone marrow-derived preosteoclasts were used as an in vitro osteoclast differentiation. This study revealed that co-cultures using ddY or ICR mouse strain responded differently to LPS while responded equally to 1α,25(OH)2D3. Thus, the different response to LPS indicates dissimilarity of two mouse stains in their capacity for generating osteoclasts while the two mouse strains share the similarity in response to 1α,25(OH)2D3. To identify which cells between osteoblasts and preosteoclasts in the co-culture are responsible for the dissimilarity, the reciprocal co-cultures were performed between ddY and ICR mouse strains. The treatment of 1,25(OH)2D3 to ddY/ICR (osteoblasts from ddY/preosteoclasts from ICR) and ICR/ddY reciprocal co-cultures also showed the similarity. In case of LPS treatment, the results of ddY/ICR were similar to ddY/ddY and the results of the other reciprocal co-culture, ICR/ddY combination, were consistent with those of ICR/ICR. It suggests that the dissimilarity between the two mouse strains may resident in osteoblasts but not in preosteoclasts. Therefore, the osteoblast is responsible for mouse strain-dependent osteoclastogenesis in response to LPS. Although mouse models will continue to provide insights into molecular mechanisms of osteoclastogenesis, caution should be exercised when using different mouse strains, especially ddY and ICR strains as models for osteoclast differentiation.
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