Journal of Microbiology

Aeryun Kim

6 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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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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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
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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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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.

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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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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
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Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model
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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

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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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
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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
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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
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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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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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