scholarly journals Disruption of gastric mucous granule exocytosis by Helicobacter pylori virulence factor CagA

2021 ◽  
Author(s):  
Ryo Ninomiya ◽  
Shuichi Kubo ◽  
Tooru Kajiwara ◽  
Hiroko Koizumi ◽  
Akinori Tokunaga ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factor ◽  
Large Scale ◽  
Mucosal Damage ◽  
Small Gtpase ◽  
Human Gastric Mucosa ◽  
Granule Exocytosis ◽  
Mucous Granule ◽  
Gastric Mucous ◽  
Mucous Barrier

Abstract Helicobacter pylori infection is the strongest known risk factor of stomach cancer. Strains harboring the virulence factor CagA (cytotoxin-associated gene A) significantly stimulate host inflammatory response, which increases the risk of ulceration and cancer. However, the mechanisms by which CagA triggers prolonged inflammation with mucosal damage remain elusive. Based on a large-scale genetic screen using Drosophila, we identified a novel CagA target Synaptotagmin-like protein 2-a, Slp2-a, an effector of small GTPase Rab27. Using gastric organoid-derived monolayers of polarized mucous cells, we demonstrated that CagA inhibited Slp2-a-mediated docking of mucous granules to the plasma membrane by direct binding to Slp2-a. We further observed aberrant cytoplasmic retention of mucus in human gastric mucosa infected with CagA-expressing strains. These results suggest that CagA could be disrupting the protective mucous barrier by inhibiting Slp2-a-mediated mucous granule exocytosis, which may lead to mucosal damage from luminal acid and pepsin to promote inflammation leading to cancer.

scholarly journals The Neutrophil-Activating Protein (Hp-Nap) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor

2000 ◽  
Vol 191 (9) ◽  
pp. 1467-1476 ◽  
Author(s):  
Barbara Satin ◽  
Giuseppe Del Giudice ◽  
Vittorina Della Bianca ◽  
Stefano Dusi ◽  
Carlo Laudanna ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factor ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Cytosolic Calcium ◽  
Interferon Γ ◽  
Human Gastric Mucosa ◽  
Oxygen Intermediates ◽  
H Pylori ◽  
Factor Α

Helicobacter pylori infection induces the appearance of inflammatory infiltrates, consisting mainly of neutrophils and monocytes, in the human gastric mucosa. A bacterial protein with neutrophil activating activity (HP-NAP) has been previously identified, but its role in infection and immune response is still largely unknown. Here, we show that vaccination of mice with HP-NAP induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-NAP, suggesting an important role of this factor in immunity. We also show that HP-NAP is chemotactic for human leukocytes and that it activates their NADPH oxidase to produce reactive oxygen intermediates, as demonstrated by the translocation of its cytosolic subunits to the plasma membrane, and by the lack of activity on chronic granulomatous disease leukocytes. This stimulating effect is strongly potentiated by tumor necrosis factor α and interferon γ and is mediated by a rapid increase of the cytosolic calcium concentration. The activation of leukocytes induced by HP-NAP is completely inhibited by pertussis toxin, wortmannin, and PP1. On the basis of these results, we conclude that HP-NAP is a virulence factor important for the H. pylori pathogenic effects at the site of infection and a candidate antigen for vaccine development.

Helicobacter pylori infection produces expression of secretory component in gastric mucous cells

2001 ◽  
Vol 120 (5) ◽  
pp. A708-A709
Author(s):  
T KANEKO ◽  
H OTA ◽  
M HAYAMA ◽  
K NAKAJIMA ◽  
A YOSHIZAWA ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Secretory Component ◽  
Helicobacter Pylori Infection ◽  
Mucous Cells ◽  
Gastric Mucous

scholarly journals Tu1497 NATIONWIDE SURVEY OF HELICOBACTER PYLORI ANTIBIOTIC RESISTANCE IN HIGH PREVALENCE OF GASTRIC CANCER COUNTRY (BHUTAN): A LARGE-SCALE COMMUNITY-BASED STUDY

2020 ◽  
Vol 91 (6) ◽  
pp. AB591-AB592
Author(s):  
Ratha-Korn Vilaichone ◽  
Natsuda Aumpan ◽  
Tomohisa Uchida ◽  
Thawee Ratanachu-ek ◽  
Lotay Tshering ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Large Scale ◽  
Nationwide Survey ◽  
Community Based ◽  
High Prevalence

Inhibition of low-density lipoprotein uptake by Helicobacter pylori virulence factor CagA

2021 ◽  
Vol 556 ◽  
pp. 192-198
Author(s):  
Ryo Ninomiya ◽  
Shuichi Kubo ◽  
Takehiro Baba ◽  
Tooru Kajiwara ◽  
Akinori Tokunaga ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Uptake

Lessons towards the roadmap on implementation and sustainability of cancer control actions

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
T Albreht
Keyword(s):  
Helicobacter Pylori ◽  
Cancer Patients ◽  
Stomach Cancer ◽  
Antibiotic Treatment ◽  
Joint Action ◽  
Large Scale ◽  
Cancer Control ◽  
Research Activity ◽  
Cancer Management ◽  
Control Actions

Abstract The speaker will present the Innovative Partnership for Action Against Cancer (iPAAC) Joint Action (JA), which is aiming to develop innovative approaches to advances in cancer control and a Roadmap on Implementation and Sustainability of Cancer Control Actions, identifying areas of relevance to AMR. The issue of AMR is an important issue in view of cancer management. It pertains both to the control of one of the pathogens clearly identified as conducive to cancer - Helicobacter pylori as well as to the issues arising from the vulnerability of the cancer patients in the course of oncological treatment. In the previous JA on Cancer Joint Action on Cancer Control (CanCon), an expert consensus process led to the conclusion that population-based screening for Helicobacter pylori, followed by antibiotic treatment at large scale could trigger AMR, even if it could offset some morbidity due to stomach cancer. It is clear that further research activity is necessary to explore this issue since stomach cancer remains a public health challenge. This is important because of late stage detection, resulting in poor survival. The other important issue is the need to protect cancer patients in treatment and beyond by securing effective antibiotic treatment for infections arising from their condition and/or following their treatment.

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