Pathogenic enablers — toxic relationships in the stomach

Wroblewski, Lydia E.; Peek, Richard M.

doi:10.1038/nrgastro.2016.68

Cited by 14 publications

(10 citation statements)

References 9 publications

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“…At least 17 genes must be expressed to encode the intact T4SS for its essential functions, and 14 genes must be expressed to fully induce IL-8 secretion [127,128]. The strains expressing the intact cag PAI are associated with the development of several disorders like chronic gastritis, peptic ulcer diseases, and gastric cancer [129,130,131,132,133]. Moreover, a recent study found that the strains recovered from the ulcer patients contained a significantly higher prevalence of all individual genes and intact cag PAI compared to strains recovered from non-ulcer patients [134].…”

Section: Virulence Factors Associated With Gastric Epithelial Cellmentioning

confidence: 99%

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Ansari

Yamaoka

2019

Toxins

174

141

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Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world’s population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism.

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Section: Virulence Factors Associated With Gastric Epithelial Cellmentioning

confidence: 99%

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Ansari

Yamaoka

2019

Toxins

174

141

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“…The relationship between HP infection and gastric carcinogenesis has been substantially demonstrated. The carcinogenicity of HP has been well established, involving the injection of CagA by type IV secretion systems [4][5][6][7] or alterations to the DNA methylome [8][9][10][11]. Importantly, several prospective studies had stated that gastric cancer develops only in patients with HP infection [12,13].…”

Section: Introductionmentioning

confidence: 99%

Endoscopic and Pathological Characteristics of <b><i>Helicobacter pylori</i></b> Infection-Negative Early Gastric Cancer

Mizutani

Araki

Saigo

et al. 2020

Dig Dis

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Background: The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. Methods: This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H+/K+ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). Results: Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types: undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H+/K+ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. Conclusion: Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin.

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“…The Hp T4SS is encoded by the cag pathogenicity island (cagPAI) and contains up to 32 genes expressing all VirB orthologs and VirD4 as well as several auxiliary factors (Backert et al, 2015). The presence of this T4SS has been associated with several disorders ranging from chronic gastritis to ulceration to gastric cancer (Wroblewski and Peek, 2016). Electron microscopy identified a 41 nm core structure (Frick-Cheng et al, 2016) and the T4SS pilus protruding from the bacterial surface (Kwok et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery

Tegtmeyer

Weßler

Necchi

et al. 2017

Cell Host & Microbe

127

149

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The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites. Hp accomplishes this by secreting another bacterial protein, the serine protease HtrA, which opens cell-to-cell junctions through cleaving epithelial junctional proteins including occludin, claudin-8, and E-cadherin. Using a genetic system expressing a peptide inhibitor, we demonstrate that HtrA activity is necessary for paracellular transmigration of Hp across polarized cell monolayers to reach basolateral membranes and inject CagA. The contribution of this unique signaling cascade to Hp pathogenesis is discussed.

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Pathogenic enablers — toxic relationships in the stomach

Cited by 14 publications

References 9 publications

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Endoscopic and Pathological Characteristics of <b><i>Helicobacter pylori</i></b> Infection-Negative Early Gastric Cancer

Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery

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