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Jeong-Heon Cha 10 Articles
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
J. Microbiol. 2022;60(8):849-858.   Published online June 22, 2022
DOI: https://doi.org/10.1007/s12275-022-2130-z
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AbstractAbstract PDF
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.

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  • 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
J. Microbiol. 2022;60(2):207-214.   Published online November 10, 2021
DOI: https://doi.org/10.1007/s12275-022-1483-7
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AbstractAbstract PDF
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.

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  • 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
J. Microbiol. 2021;59(12):1125-1132.   Published online October 31, 2021
DOI: https://doi.org/10.1007/s12275-021-1450-8
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AbstractAbstract PDF
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 5􍿁􀁇region 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

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  • 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
DOI: https://doi.org/10.1007/s12275-021-1136-2
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AbstractAbstract PDF
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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AbstractAbstract PDF
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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  • N-acetylcysteine enhances antioxidant capacity and anti-bacterial immunity of T cells in tilapia by regulating KEAP1-NRF2 axis
    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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AbstractAbstract PDF
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.

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  • 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
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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AbstractAbstract PDF
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.

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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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AbstractAbstract PDF
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.

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    Meenu Saini, Amuliya Kashyap, Shruti Bindal, Kuldeep Saini, Rani Gupta
    Frontiers in Microbiology.2021;[Epub]     CrossRef
  • Quantitative analysis of γ-glutamylpeptides by liquid chromatography-mass spectrometry and application for γ-glutamyltransferase assays
    Sho Kobayashi, Yoshinori Tokairin, Takeru Miyakoshi, Takuya Saito, Keita Nagaoka, Yoshitaka Ikeda, Junichi Fujii, Hiroyuki Konno
    Analytical Biochemistry.2019; 578: 13.     CrossRef
  • Isolation of γ-Glutamyl-Transferase Rich-Bacteria from Mouse Gut by a Near-Infrared Fluorescent Probe with Large Stokes Shift
    Tao Liu, Qiu-Long Yan, Lei Feng, Xiao-Chi Ma, Xiang-Ge Tian, Zhen-Long Yu, Jing Ning, Xiao-Kui Huo, Cheng-Peng Sun, Chao Wang, Jing-Nan Cui
    Analytical Chemistry.2018; 90(16): 9921.     CrossRef
  • Heterologous expression and enzymatic characterization of γ-glutamyltranspeptidase from Bacillus amyloliquefaciens
    Jung-Min Lee, Jaejung Lee, Gyeong-Hwa Nam, Byung-Sam Son, Myoung-Uoon Jang, So-Won Lee, Byung-Serk Hurh, Tae-Jip Kim
    Journal of Microbiology.2017; 55(2): 147.     CrossRef
  • Scientific Opinion on the update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA†
    Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies, Rosina Girones, Lieve Herman, Konstantinos Koutsoumanis, Roland Lindqvist, Birgit Nørrung, Lucy Robertson, Giuseppe Ru, Moez Sanaa, Marion Simmons, Panagiotis Skandamis, Emma Snar
    EFSA Journal.2017;[Epub]     CrossRef
Complementation System for Helicobacter pylori
Jinmoon Kim , Sung-Whan Kim , Sungil Jang , D. Scott Merrell , Jeong-Heon Cha
J. Microbiol. 2011;49(3):481-486.   Published online June 30, 2011
DOI: https://doi.org/10.1007/s12275-011-1196-9
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AbstractAbstract PDF
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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  • AI-2 Induces Urease Expression Through Downregulation of Orphan Response Regulator HP1021 in Helicobacter pylori
    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
Ho Gil Choi , Jin Moon Kim , Bong-Ju Kim , Yun-Jung Yoo , Jeong-Heon Cha
J. Microbiol. 2007;45(6):566-571.
DOI: https://doi.org/2607 [pii]
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AbstractAbstract PDF
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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