High Resolution Electron Microscopy of the &lt;em&gt;Helicobacter pylori&lt;/em&gt; Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability

Haley, Kathryn P.; Blanz, Eric Joshua; Gaddy, Jennifer A.

doi:10.3791/52122-v

Cited by 3 publications

(3 citation statements)

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“…Helicobacter pylori (H. pylori) is a microaerophilic, motile, non-sporulating Gram-negative bacillary bacterium, containing 5 to 7 sheathed unipolar flagella (Picture 1) (LIMA, 2009;HALEY et al, 2014). H. pylori was isolated for the first time in Australia in 1983, from gastric biopsy fragments from patients with chronic gastritis and peptic ulcers, and won Warren and Marshall the 2005 Nobel Prize in Medicine.…”

Section: Helicobacter Pylorimentioning

confidence: 99%

Association of Helicobacter Pylori With the Lewis Antigen: A Literature Review

Prestes,

Bier,

Luz

et al. 2023

JHS

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Since the 90s, several studies have presented the probable relationship between antigens of the ABO-Lewis system and susceptibility to infections, as they end up serving as receptors or co-receptors for these microorganisms. This literary review study aimed to demonstrate the correlation between the pathogenesis of infection by Helicobacter pylori and the Lewis blood system, in order to spread knowledge of the importance of blood phenotypes to health professionals. Data collection was carried out using the PubMed and SciELO reference bases over a period of 20 years (2002 -2022) with the terms "Blood type", "Lewis system", "ABO system'' , "H. Pylori", "Helicobacter pylori. " Helicobacter pylori binds to the antigen Lewis b (Le b), rich in fucose and expressed on the surface of gastric epithelial cells. Furthermore, Le b has high affinity for BabA adhesins, one of the virulence factors of this genus of bacteria that infect humans and promote chronic inflammation and/or other gastric diseases. Since infection by this microorganism is characterized by chronicity, knowledge of its pathogenesis and correlation with all types of risk factors is an important prevention mechanism.

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Section: Helicobacter Pylorimentioning

confidence: 99%

Association of Helicobacter Pylori With the Lewis Antigen: A Literature Review

Prestes,

Bier,

Luz

et al. 2023

JHS

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“…The cagT4SS proteins are unique to H. pylori and inhibitors would therefore not target other bacteria of the microbiome. We have chosen the essential ATPase Cagα as a target (14,38,39). Cagα is a hexameric ATPase that localizes at the inner membrane and is a homolog of VirB11 proteins that are conserved and essential for all T4SS.…”

Section: Introductionmentioning

confidence: 99%

Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori

Morin,

Verma,

Arya

et al. 2024

Biochem. Cell Biol.

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We here describe the structure-based design of small molecule inhibitors of the type IV secretion system of Helicobacter pylori. The secretion system is encoded by the cag pathogenicity island, and we chose Cagα, a hexameric ATPase and member of the family of VirB11-like proteins, as target for inhibitor design. We first solved the crystal structure of Cagα in a complex with the previously identified small molecule inhibitor 1G2. The molecule binds at the interface between two Cagα subunits and mutagenesis of the binding site identified Cagα residues F39 and R73 as critical for 1G2 binding. Based on the inhibitor binding site we synthesized 98 small molecule derivates of 1G2 to improve binding of the inhibitor. We used the production of interleukin-8 of gastric cancer cells during H. pylori infection to screen the potency of inhibitors and we identified five molecules (1G2_1313, 1G2_1338, 1G2_2886, 1G2_2889 and 1G2_2902) that have similar or higher potency than 1G2. Differential scanning fluorimetry suggested that these five molecules bind Cagα, and enzyme assays demonstrated that some are more potent ATPase inhibitors than 1G2. Finally, scanning electron microscopy revealed that 1G2 and its derivatives inhibit the assembly of T4SS-determined extracellular pili suggesting a mechanism for their anti-virulence effect.

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“…The cag T4SS proteins are unique to H. pylori and inhibitors would therefore not target other bacteria of the microbiome. We have chosen the essential ATPase Cagα as a target (14,38,39). Cagα is a hexameric ATPase that localizes at the inner membrane and is a homolog of VirB11 proteins that are conserved and essential for all T4SS.…”

Section: Introductionmentioning

confidence: 99%

Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori

Morin,

Verma,

Arya

et al. 2023

Preprint

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We here describe the structure-based design of small molecule inhibitors of the type IV secretion system ofHelicobacter pylori. The secretion system is encoded by the□cag□pathogenicity island, and we chose Cagα, a hexameric ATPase and member of the family of VirB11-like proteins, as target for inhibitor design. We first solved the crystal structure of Cagα in a complex with the previously identified small molecule inhibitor 1G2. The molecule binds at the interface between two Cagα subunits and mutagenesis of the binding site identified Cagα residues F39 and R73 as critical for 1G2 binding. Based on the inhibitor binding site we synthesized 98 small molecule derivates of 1G2 to improve binding of the inhibitor. We used the production of interleukin-8 of gastric cancer cells duringH. pyloriinfection to screen the potency of inhibitors and we identified five molecules (1G2_1313, 1G2_1338, 1G2_2886, 1G2_2889 and 1G2_2902) that have similar or higher potency than 1G2. Differential scanning fluorimetry suggested that these five molecules bind Cagα, and enzyme assays demonstrated that some are more potent ATPase inhibitors than 1G2. Finally, scanning electron microscopy revealed that 1G2 and its derivatives inhibit the assembly of T4SS-determined extracellular pili suggesting a mechanism for their anti-virulence effect.

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High Resolution Electron Microscopy of the <em>Helicobacter pylori</em> Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability

Cited by 3 publications

References 0 publications

Association of Helicobacter Pylori With the Lewis Antigen: A Literature Review

Association of Helicobacter Pylori With the Lewis Antigen: A Literature Review

Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori

Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori

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