- Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
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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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 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.
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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
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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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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.
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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
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Yun Hui Choi , Jing Lai , Myeong-A Kim , Aeryun Kim , Jinmoon Kim , Hanfu Su , Linhu Ge , Jeong-Heon Cha
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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
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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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Citations
Citations to this article as recorded by - 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
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