Composition, Structure and Function of the
            <i>Helicobacter Pylori cag</i>
            Pathogenicity Island Encoded type IV Secretion System

Backert, Steffen; Tegtmeyer, Nicole; Fischer, Wolfgang

doi:10.2217/fmb.15.32

Cited by 174 publications

(165 citation statements)

References 65 publications

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“…intestini . ABC transporters and type IV secretion systems have been reported to be involved in the cross talk between endosymbionts and their insect hosts [17, 21, 27–28]. Multiple CDSs associated to ABC transporters were identified (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Illeghems

Kerrebroeck

et al. 2016

PLoS ONE

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The whole-genome sequence of Bombella intestini LMG 28161T, an endosymbiotic acetic acid bacterium (AAB) occurring in bumble bees, was determined to investigate the molecular mechanisms underlying its metabolic capabilities. The draft genome sequence of B. intestini LMG 28161T was 2.02 Mb. Metabolic carbohydrate pathways were in agreement with the metabolite analyses of fermentation experiments and revealed its oxidative capacity towards sucrose, D-glucose, D-fructose and D-mannitol, but not ethanol and glycerol. The results of the fermentation experiments also demonstrated that the lack of effective aeration in small-scale carbohydrate consumption experiments may be responsible for the lack of reproducibility of such results in taxonomic studies of AAB. Finally, compared to the genome sequences of its nearest phylogenetic neighbor and of three other insect associated AAB strains, the B. intestini LMG 28161T genome lost 69 orthologs and included 89 unique genes. Although many of the latter were hypothetical they also included several type IV secretion system proteins, amino acid transporter/permeases and membrane proteins which might play a role in the interaction with the bumble bee host.

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Section: Resultsmentioning

confidence: 99%

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Illeghems

Kerrebroeck

et al. 2016

PLoS ONE

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“…When cagA is transported into the epithelial cells of host gastric mucosa by type IV secretion system encoded by CagPAI, a tyrosine residue on it becomes phosphorylated. Interacting with a variety of proteins of the host cells, CagA amplifies, causing a change in the morphology of gastric epithelial cells (Figure 4)[23,24]. In recent years, polymorphisms of cagA was revealed to encode four proteins like A, B, C, and D, which play a key role in cytoskeletal rearrangement, infiltration and cell proliferation.…”

Section: Polymorphisms Of H Pylori Virulence Genesmentioning

confidence: 99%

Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal diseases

Chen¹,

Mo²,

Huang³

et al. 2016

WJG

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Helicobacter pylori (H. pylori) is a kind of chronic infectious pathogen which can cause chronic gastritis, peptic ulcer, gastric cancer and other diseases. The genetic structure of the pathogenic genes of H. pylori varies largely, which contributes to the differences in virulence among various strains, and in clinical symptoms. Virulence genes of H. pylori can be categorized into three main classes: those related to adhesion and colonization, those related to gastric mucosal injury, and others. This review focuses on the relationship between genetic polymorphisms of the three classes of virulence genes of H. pylori and diseases. Most of the genetic polymorphisms of the main virulence factors of H. pylori are summarized in this paper.

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“…2). T4SS delivery occurs via several steps, including assembly of the T4SS pilus, binding of the pilus to its host cell target, and active protein secretion (42). The imaA phenotype did not depend on CagA per se, suggesting that ImaA acts at one of the steps that are CagA independent, such as binding or assembly.…”

Section: Discussionmentioning

confidence: 99%

The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α ₅ β ₁ Integrin

et al. 2017

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The human pathogen Helicobacter pylori uses the host receptor ␣ 5 ␤ 1 integrin to trigger inflammation in host cells via its cag pathogenicity island (cag PAI) type IV secretion system (T4SS). Here, we report that the H. pylori ImaA protein (HP0289) decreases the action of the cag PAI T4SS via tempering the bacterium's interaction with ␣ 5 ␤ 1 integrin. Previously, imaA-null mutants were found to induce an elevated inflammatory response that was dependent on the cag PAI T4SS; here we extend those findings to show that the elevated response is independent of the CagA effector protein. To understand how ImaA could be affecting cag PAI T4SS activity at the host cell interface, we utilized the Phyre structural threading program and found that ImaA has a region with remote homology to bacterial integrinbinding proteins. This region was required for ImaA function. Unexpectedly, we observed that imaA mutants bound higher levels of ␣ 5 ␤ 1 integrin than wild-type H. pylori, an outcome that required the predicted integrin-binding homology region of ImaA. Lastly, we report that ImaA directly affected the amount of host cell ␤1 integrin but not other cellular integrins. Our results thus suggest a model in which H. pylori employs ImaA to regulate interactions between integrin and the T4SS and thus alter the host inflammatory strength.KEYWORDS autotransporter proteins, inflammation, pathogenesis, secretion systems, virulence factors T he human pathogen Helicobacter pylori is one of the world's most common pathogens, chronically colonizing the stomachs of at least one-third of the world's population, with the populations of many countries experiencing rates of colonization of over 50% (1, 2). The outcomes of this infection vary on the basis of a combination of bacterial genetics, host genetics, and environmental factors (3). Ten to 15% of those infected go on to develop severe diseases, including ulcers and gastric adenocarcinoma (4-6). H. pylori-triggered diseases cause significant mortality and morbidity worldwide. For example, gastric adenocarcinoma killed over 700,000 people worldwide in 2012, and in the United States, 26,370 people were expected to have been diagnosed with this disease in 2016 (7,8).One of the main factors that influences the H. pylori disease outcome is whether a person is infected with a strain that possesses the cytotoxin-associated gene (cag) pathogenicity island (cag PAI). cag PAI-positive strains are associated with severe inflammation, peptic ulcers, and gastric cancer (9). The cag PAI encodes a type IV secretion system (T4SS), a large multiprotein system that triggers a host inflammatory response directly via interactions with the host cells (10) and also via delivery of proinflammatory cargo: the protein CagA and the bacterial molecule peptidoglycan (11,12).Given the cost and consequence of producing an active cag PAI T4SS, its function is controlled at several levels (2, 13, 14). While there is some transcriptional modulation

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Composition, Structure and Function of the Helicobacter Pylori cag Pathogenicity Island Encoded type IV Secretion System

Cited by 174 publications

References 65 publications

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal diseases

The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α ₅ β ₁ Integrin

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Composition, Structure and Function of the Helicobacter Pylori cag Pathogenicity Island Encoded type IV Secretion System

Cited by 174 publications

References 65 publications

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Whole-Genome Sequence Analysis of Bombella intestini LMG 28161T, a Novel Acetic Acid Bacterium Isolated from the Crop of a Red-Tailed Bumble Bee, Bombus lapidarius

Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal diseases

The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α 5 β 1 Integrin

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Product

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The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α ₅ β ₁ Integrin