| Title | Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA |
|---|---|
| Author | Kavinda Tissera1,2,3, Myeong-A Kim2, Jing Lai2, Sacheera Angulmaduwa2, Aeryun Kim4, D. Scott Merrell5, Ji-Hye Kim6*, Hanfu Su1*, and Jeong-Heon Cha1,2* |
| Address | 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 Korea |
| Bibliography | Journal of Microbiology, 60(2),207-214, 2022, |
| DOI | 10.1007/s12275-022-1483-7 |
| Key Words | Helicobacter pylori, cagA, polymorphism, EPIYA-C motif, geographic diversity |
| 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. |