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

doi:10.1007/s12275-022-1483-7

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Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA: Kavinda Tissera ^1,2,3, Myeong-A Kim ², Jing Lai ², Sacheera Angulmaduwa ², Aeryun Kim ⁴, D. Scott Merrell ⁵, Ji-Hye Kim ⁶, Hanfu Su ¹, Jeong-Heon Cha ^1,2; Journal of Microbiology 2022;60(2):207-214.
DOI: https://doi.org/10.1007/s12275-022-1483-7
Published online: November 10, 2021

¹Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong 510182, P. R. China, ²Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea, ³Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Ruhuna, Galle 80000, Sri Lanka, ⁴Department of Dental Hygiene, Gangdong University, Eumseong 27600, Republic of Korea, ⁵Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA, ⁶Department of Dental Hygiene, Baekseok University, Cheonan 31065, Republic of Korea¹Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong 510182, P. R. China, ²Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea, ³Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Ruhuna, Galle 80000, Sri Lanka, ⁴Department of Dental Hygiene, Gangdong University, Eumseong 27600, Republic of Korea, ⁵Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA, ⁶Department of Dental Hygiene, Baekseok University, Cheonan 31065, Republic of Korea

Corresponding author: Ji-Hye Kim , Tel: +82-2-2228-3061,
Hanfu Su , Tel: +82-2-2228-3061,
Jeong-Heon Cha , Tel: +82-2-2228-3061,

Received: 15 September 2021 • Revised: 20 October 2021 • Accepted: 21 October 2021

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Abstract

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.

Keywords: FGF11;FGFR-dependent;cell proliferation;intracrine FGF;mitogenesis

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Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA

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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