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Creation and Initial Characterization of Isogenic Helicobacter pylori CagA EPIYA Variants Reveals Differential Activation of Host Cell Signaling Pathways

Authors
 Dacie R. Bridge  ;  Faith C. Blum  ;  Sungil Jang  ;  Jinmoon Kim  ;  Jeong-Heon Cha  ;  D. Scott Merrell 
Citation
 SCIENTIFIC REPORTS, Vol.7(1) : 11057, 2017 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2017
Abstract
The polymorphic CagA toxin is associated with Helicobacter pylori-induced disease. Previous data generated using non-isogenic strains and transfection models suggest that variation surrounding the C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs as well as the number of EPIYA motifs influence disease outcome. To investigate potential CagA-mediated effects on host cell signaling, we constructed and characterized a large panel of isogenic H. pylori strains that differ primarily in the CagA EPIYA region. The number of EPIYA-C motifs or the presence of an EPIYA-D motif impacted early changes in host cell elongation; however, the degree of elongation was comparable across all strains at later time points. In contrast, the strain carrying the EPIYA-D motif induced more IL-8 secretion than any other EPIYA type, and a single EPIYA-C motif induced comparable IL-8 secretion as isolates carrying multiple EPIYA-C alleles. Similar levels of ERK1/2 activation were induced by all strains carrying a functional CagA allele. Together, our data suggest that polymorphism in the CagA C-terminus is responsible for differential alterations in some, but not all, host cell signaling pathways. Notably, our results differ from non-isogenic strain studies, thus highlighting the importance of using isogenic strains to study the role of CagA toxin polymorphism in gastric cancer development.
Files in This Item:
T201703840.pdf Download
DOI
10.1038/s41598-017-11382-y
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Jang, Sungil(장성일) ORCID logo https://orcid.org/0000-0001-6144-6899
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160998
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