Creation and Initial Characterization of Isogenic Helicobacter pylori CagA EPIYA Variants Reveals Differential Activation of Host Cell Signaling Pathways.
Sci Rep
; 7(1): 11057, 2017 09 08.
Article
em En
| MEDLINE
| ID: mdl-28887533
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Transdução de Sinais
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Helicobacter pylori
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Motivos de Aminoácidos
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Células Epiteliais
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Proteínas Mutantes
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Interações Hospedeiro-Patógeno
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Antígenos de Bactérias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article