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Lactobacillus gasseri Suppresses the Helicobacter pylori-Induced Hummingbird Phenotype by Inhibiting CagA Phosphorylation and SHP-2 Interaction
by
Jonsson, Ann-Beth
, Somiah, Tanvi
, Gupta, Rajesh K.
, Steinlein, Amelia C.
in
Aldehydes
/ Antigens, Bacterial - genetics
/ Antigens, Bacterial - metabolism
/ Bacteria
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Birds
/ CagA
/ Cell Line, Tumor
/ cell morphology
/ Cells
/ Cytokines
/ Epithelial Cells - metabolism
/ Epithelial Cells - microbiology
/ Ethylenediaminetetraacetic acid
/ Genetic aspects
/ Genotype & phenotype
/ Health aspects
/ Helicobacter infections
/ Helicobacter Infections - metabolism
/ Helicobacter Infections - microbiology
/ Helicobacter pylori
/ Helicobacter pylori - metabolism
/ Helicobacter pylori - pathogenicity
/ Host-Pathogen Interactions
/ Humans
/ Infection
/ Kinases
/ Lactobacillus
/ Lactobacillus - physiology
/ Localization
/ Morphology
/ Motility
/ Phenotype
/ Phosphatase
/ Phosphorylation
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
/ Signal Transduction
/ Stomach cancer
/ Virulence
/ Virulence (Microbiology)
2025
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Lactobacillus gasseri Suppresses the Helicobacter pylori-Induced Hummingbird Phenotype by Inhibiting CagA Phosphorylation and SHP-2 Interaction
by
Jonsson, Ann-Beth
, Somiah, Tanvi
, Gupta, Rajesh K.
, Steinlein, Amelia C.
in
Aldehydes
/ Antigens, Bacterial - genetics
/ Antigens, Bacterial - metabolism
/ Bacteria
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Birds
/ CagA
/ Cell Line, Tumor
/ cell morphology
/ Cells
/ Cytokines
/ Epithelial Cells - metabolism
/ Epithelial Cells - microbiology
/ Ethylenediaminetetraacetic acid
/ Genetic aspects
/ Genotype & phenotype
/ Health aspects
/ Helicobacter infections
/ Helicobacter Infections - metabolism
/ Helicobacter Infections - microbiology
/ Helicobacter pylori
/ Helicobacter pylori - metabolism
/ Helicobacter pylori - pathogenicity
/ Host-Pathogen Interactions
/ Humans
/ Infection
/ Kinases
/ Lactobacillus
/ Lactobacillus - physiology
/ Localization
/ Morphology
/ Motility
/ Phenotype
/ Phosphatase
/ Phosphorylation
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
/ Signal Transduction
/ Stomach cancer
/ Virulence
/ Virulence (Microbiology)
2025
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Lactobacillus gasseri Suppresses the Helicobacter pylori-Induced Hummingbird Phenotype by Inhibiting CagA Phosphorylation and SHP-2 Interaction
by
Jonsson, Ann-Beth
, Somiah, Tanvi
, Gupta, Rajesh K.
, Steinlein, Amelia C.
in
Aldehydes
/ Antigens, Bacterial - genetics
/ Antigens, Bacterial - metabolism
/ Bacteria
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Birds
/ CagA
/ Cell Line, Tumor
/ cell morphology
/ Cells
/ Cytokines
/ Epithelial Cells - metabolism
/ Epithelial Cells - microbiology
/ Ethylenediaminetetraacetic acid
/ Genetic aspects
/ Genotype & phenotype
/ Health aspects
/ Helicobacter infections
/ Helicobacter Infections - metabolism
/ Helicobacter Infections - microbiology
/ Helicobacter pylori
/ Helicobacter pylori - metabolism
/ Helicobacter pylori - pathogenicity
/ Host-Pathogen Interactions
/ Humans
/ Infection
/ Kinases
/ Lactobacillus
/ Lactobacillus - physiology
/ Localization
/ Morphology
/ Motility
/ Phenotype
/ Phosphatase
/ Phosphorylation
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
/ Signal Transduction
/ Stomach cancer
/ Virulence
/ Virulence (Microbiology)
2025
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Lactobacillus gasseri Suppresses the Helicobacter pylori-Induced Hummingbird Phenotype by Inhibiting CagA Phosphorylation and SHP-2 Interaction
Journal Article
Lactobacillus gasseri Suppresses the Helicobacter pylori-Induced Hummingbird Phenotype by Inhibiting CagA Phosphorylation and SHP-2 Interaction
2025
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Overview
Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. The bacterium leverages several unique virulence factors to its advantage in order to colonize the human host. Among these, T4SS-delivered cytotoxin-associated gene A (CagA) has the most well-established links to severe forms of disease. To explore the effect of lactobacilli in disrupting CagA functions within host cells, we expressed HA-tagged humanized cagA in the human gastric epithelial AGS cell line and studied both the phosphorylation levels of CagA and its downstream binding partners. We found that gastric-specific Lactobacillus gasseri Kx110 A1 suppressed the phosphorylation of CagA and inhibited phosphorylation-dependent downstream signaling, resulting in the suppression of CagA-induced cell elongation of AGS cells, commonly known as the hummingbird phenotype. Surprisingly, phosphorylation-independent signaling was unaffected by L. gasseri. Furthermore, our confocal microscopy analysis revealed that CagA was mislocalized to the cytoplasm, suggesting that L. gasseri interferes with its membrane localization and thereby hinders its phosphorylation. Live L. gasseri that had direct contact with host cells was found to be necessary to suppress the hummingbird phenotype. In summary, the data suggest that a L. gasseri strain can inhibit CagA phosphorylation and suppress cell elongation.
Publisher
MDPI AG,MDPI
Subject
/ Antigens, Bacterial - genetics
/ Antigens, Bacterial - metabolism
/ Bacteria
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Birds
/ CagA
/ Cells
/ Epithelial Cells - metabolism
/ Epithelial Cells - microbiology
/ Ethylenediaminetetraacetic acid
/ Helicobacter Infections - metabolism
/ Helicobacter Infections - microbiology
/ Helicobacter pylori - metabolism
/ Helicobacter pylori - pathogenicity
/ Humans
/ Kinases
/ Motility
/ Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
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