Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC1

Kim, Ik Jung; Lee, Jeongmin; Oh, Se H.; Yoon, Mee Sup; Jang, Seyong; Holland, Robin L.; Reno, Michael L.; Hamad, Mohammed N.; Maeda, Tatsuya; Chung, Hee Jung; Chen, Jiawen; Blanke, Steven R.

doi:10.1016/j.chom.2018.04.006

Cited by 54 publications

(41 citation statements)

References 67 publications

(105 reference statements)

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“…Degradation of the ferritin in lysosome results in the better establishment of H. pylori infection and the mechanism explains its persistence in the gastric epithelial mucosa of the human stomach. 139 As per the latest report by Kim et al, 140 VacA exotoxin, that is secreted by H. pylori, stimulates the improper functioning of mitochondria. Nevertheless, it is still unclear at what extent the mitochondrial distress caused by VacA modulates the total metabolism of the host cell.…”

Section: Modulation Of Host Cell Metabolism By H Pylorimentioning

confidence: 83%

“…As per the latest report by Kim et al, VacA exotoxin, that is secreted by H. pylori , stimulates the improper functioning of mitochondria. Nevertheless, it is still unclear at what extent the mitochondrial distress caused by VacA modulates the total metabolism of the host cell .…”

Section: Manipulation Of Pattern Recognition Receptorsmentioning

confidence: 99%

“…Nevertheless, it is still unclear at what extent the mitochondrial distress caused by VacA modulates the total metabolism of the host cell . They have stated that upon H. pylori infection, the secretion of VacA indirectly alters the amino‐acid homeostasis of the host cell by which the mammalian target of rapamycin complex 1 (mTORC1), a central player in amino acid homeostasis, gets inhibited and this consequently leads to autophagy. The association of mTORC1 with lysosomal surface gets dissociated in the presence of VacA‐intoxicated Hp infection, which induces amino acid starvation and further activates the autophagy via a complex of Unc 51‐like kinase 1 …”

Section: Manipulation Of Pattern Recognition Receptorsmentioning

confidence: 99%

“…The association of mTORC1 with lysosomal surface gets dissociated in the presence of VacA-intoxicated Hp infection, which induces amino acid starvation and further activates the autophagy via a complex of Unc 51-like kinase 1. 140,141 H. pylori infection also triggers the scarcity of micronutrients like vitamins (vitamin B12, vitamin A, vitamin C, and folic acid, etc) and minerals. The presence of H. pylori in the host weakens the absorption of vitamin B12 from food, which eventually leads to pernicious anemia.…”

Section: Modulation Of Host Cell Metabolism By H Pylorimentioning

confidence: 99%

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Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Gupta

Maurya

Verma

et al. 2019

J of Cellular Biochemistry

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Helicobacter pylori and humans have one of the most complex relationships in nature. How a bacterium manages to live in one of the harshest and hostile environments is a topic of unraveling mysteries. H. pylori is a prevalent species and it colonizes the human gut of more than 50% of the world population. It infects the epithelial region of antrum and persists there for a long period. Over the time of evolution, H. pylori has developed complex strategies to extend the degree of inflammation in gastric mucosa. H. pylori needs specific adaptations for initial colonization into the host environment like helical shape, flagellar movement, chemotaxis, and the production of urease enzyme that neutralizes acidic environment of the stomach. There are several factors from the bacterium as well as from the host that participate in these complex interactions. On the other hand, to establish the persistent infection, H. pylori escapes the immune system by mimicking the host antigens. This pathogen has the ability to dodge the immune system and then persist there in the form of host cell, which leads to immune tolerance. H. pylori has an ability to manipulate its own pathogen‐associated molecular patterns, which leads to an inhibition in the binding with specific pattern recognition receptors of the host to avoid immune cell detection. Also, it manipulates the host metabolic homeostasis in the gastric epithelium. Besides, it has several genes, which may get involved in the acquisition of nutrition from the host to survive longer in the host. Due to the persistence of H. pylori, it causes chronic inflammation and raises the chances of gastric cancer. This review highlights the important elements, which are certainly responsible for the persistence of H. pylori in the human host.

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Section: Modulation Of Host Cell Metabolism By H Pylorimentioning

confidence: 83%

Section: Manipulation Of Pattern Recognition Receptorsmentioning

confidence: 99%

Section: Manipulation Of Pattern Recognition Receptorsmentioning

confidence: 99%

Section: Modulation Of Host Cell Metabolism By H Pylorimentioning

confidence: 99%

See 2 more Smart Citations

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Gupta

Maurya

Verma

et al. 2019

J of Cellular Biochemistry

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“…However, the mechanism by which these virulence factors induce autophagy remains to be investigated. One clue is that VacA damages mitochondrial function and causes nutrient depletion which may be linked to inhibition of mTOR signaling and induction of autophagy [107].…”

Section: H Pylori Infects Gastric Epithelial Cellsmentioning

confidence: 99%

Cellular evasion strategies of Helicobacter pylori in regulating its intracellular fate

Sit

Chen

et al. 2020

Seminars in Cell & Developmental Biology

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A B S T R A C THelicobacter pylori colonizes human stomach mucosa and its infection causes gastrointestinal diseases with variable severity. Bacterial infection stimulates autophagy, which is a part of innate immunity used to eliminate intracellular pathogens. Several intracellular bacteria have evolved multipronged strategies to circumvent this conserved system and thereby enhance their chance of intracellular survival. Nonetheless, studies on H. pylori have produced inconsistent results, showing either elevated or reduced clearance efficiency of intracellular bacteria through autophagy. In this review, we summarize recent studies on the mechanisms involved in autophagy induced by H. pylori and the fate of intracellular bacteria.

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Helicobacter pylori promote inflammation and host defense through the cagA‐dependent activation of mTORC1

Feng

Chen

2020

Journal Cellular Physiology

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Mechanistic target of rapamycin complex 1 (mTORC1) functions as regulating different cellular processes, including cell growth, proliferation, motility, survival, metabolism, autophagy, and protein transcription. Recently, it also found to be associated with many infections and inflammatory diseases, playing complex roles in pathogens growth and inflammation regulation. However, the regulation mechanism of mTORC1 in gastric epithelial cells and its role in Helicobacter pylori (H. pylori) infection and related gastritis remain unclear. Here, we identified that the phosphorylation of mechanistic target of rapamycin (mTOR) and the expression of DEP domain‐containing mTOR‐interacting protein (DEPTOR) was increased in gastric mucosa of H. pylori‐infected patients and mice, as well as in H. pylori‐infected gastric epithelial cells, which were largely depended on H. pylori cagA. The expression of DEPTOR was regulated via mTORC1, but, in turn, inhibited mTORC1. Knockdown mTOR significantly decreased expression and secretion of cytokines tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6, chemokines CCL7 and CXCL16, and antimicrobial peptide LL37 in vitro, while knockdown DEPTOR had the opposite effect. Similar observations were made using mTOR knockout (KO) mice in vivo, moreover. The gastric inflammation was attenuated, while the bacterial burden was increased in mTOR KO mice during H. pylori infection. These findings supported H. pylori promote gastritis and inhibit bacterial colonization through the cagA‐dependent activation of mTORC1.

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Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC1

Cited by 54 publications

References 67 publications

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Cellular evasion strategies of Helicobacter pylori in regulating its intracellular fate

Helicobacter pylori promote inflammation and host defense through the cagA‐dependent activation of mTORC1

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