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

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Název: Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
Autoři: Hanfu Su, Aeryun Kim, Jing Lai, Ji-Hye Kim, D. Scott Merrell, Sacheera Angulmaduwa, Myeong-A Kim, Kavinda Tissera, Jeong Heon Cha
Přispěvatelé: Kavinda Tissera, Myeong-A Kim, Jing Lai, Sacheera Angulmaduwa, Aeryun Kim, D Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha, Cha, Jung Heon
Zdroj: Journal of Microbiology. 60:207-214
Informace o vydavateli: The Microbiological Society of Korea, 2021.
Rok vydání: 2021
Témata: DNA, Bacterial, 0301 basic medicine, Far East, Genotype, Virulence Factors, Amino Acid Motifs, Bacterial Typing Techniques / methods, Bacterial Proteins / genetics, Helicobacter Infections, 03 medical and health sciences, Helicobacter pylori / genetics, Genetic, Bacterial Proteins, Republic of Korea, geographic diversity, Humans, Antigens, Polymorphism, Phylogeny, cagA, Antigens, Bacterial, 0303 health sciences, Genome, Polymorphism, Genetic, Helicobacter pylori, Helicobacter pylori / metabolism, Virulence Factors / genetics, Asia, Eastern, Bacterial, Bacterial / genetics, DNA, Bacterial Typing Techniques, Helicobacter Infections / microbiology, EPIYA-C motif, Helicobacter pylori / classification, Genome, Bacterial
Popis: 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 1976-3794
1225-8873
DOI: 10.1007/s12275-022-1483-7
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/34757586
https://link.springer.com/article/10.1007/s12275-022-1483-7
https://pubmed.ncbi.nlm.nih.gov/34757586/
Rights: Springer Nature TDM
CC BY NC ND
Přístupové číslo: edsair.doi.dedup.....929b29393076969976e54e3bd83019c2
Databáze: OpenAIRE
Popis
Abstrakt: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.
ISSN:19763794
12258873
DOI:10.1007/s12275-022-1483-7