Cag Type IV Secretion System: CagI Independent Bacterial Surface Localization of CagA

Kumar, Navin; Shariq, Mohd; Kumari, Rajesh; Tyagi, Rakesh K.; Mukhopadhyay, Gauranga

doi:10.1371/journal.pone.0074620

Cited by 24 publications

(49 citation statements)

References 43 publications

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“…1A, fractionated cell samples were subjected to WB using anti-CagU, anti-CagT, anti-CagI, and anti-SSB antibodies. As expected, CagT was exclusively detected in the TM fraction [31], CagI was present both in the soluble and membrane fractions [28], and SSB was detected in the C/P fraction [32]. Like CagT, CagU was detected only in the TM suggesting that CagU might exist as a membrane-associated protein.…”

Section: Cagu Is An Inner Membrane Proteinsupporting

confidence: 73%

“…Previously, we have hypothesized that CagA translocation into the host cells could be a two‐step process . Therefore, to test whether CagA can reach bacterial cell surface in the absence of CagU, we performed IFM on the wild‐type H. pylori, Hp Δ cagU , and Hp Δ cagU/cagU strains.…”

Section: Resultsmentioning

confidence: 99%

“…Next, we focused our attention to test the role of CagU in the surface localization of CagA. In this connection, we have previously hypothesized that CagA translocation into the host epithelial cells could be a two-step process, since CagA can reach the bacterial cell surface in the absence of Cag-T4SS pilus (in the absence of CagI in HpDcagI strain) [28]. We have demonstrated here that CagA surface localization is CagU dependent, like in the case of CagE [18].…”

Section: Discussionmentioning

confidence: 99%

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Biochemical characterization of the Helicobacter pylori Cag‐type IV secretion system unique component CagU

et al. 2017

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Many strains of Helicobacter pylori encode a protein secreting type IV secretion system called the Cag-T4SS. Here, we characterize one of the Cag-T4SS-specific components, CagU (HP0531). We report that CagU is a bacterial inner membrane-associated protein, partially processed at the C terminus, and that it interacts with the VirB6 and VirB8 homologs CagW and CagV, respectively. The level of expression of CagU is partially affected in the absence of cagX, cagW, and cagV. Deletion of cagU aborts surface localization of CagA and affects the expression levels of CagI and CagH, which are involved in the Cag-T4SS pilus formation. Complementation of the cagU null mutation by wild-type cagU restores all these functions, suggesting its importance for Cag-T4SS function.

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Section: Cagu Is An Inner Membrane Proteinsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Biochemical characterization of the Helicobacter pylori Cag‐type IV secretion system unique component CagU

et al. 2017

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“…Polyclonal antibodies against Cag proteins such as Cagδ, CagH, CagL, CagE, CagY, CagZ, CagX, CagT, CagM, CagI, and CagF were raised by immunization of rabbit and mice in the laboratory as described previously . Briefly, to generate polyclonal antibody against CagV, a full‐length cagV was cloned in pET‐28a vector and overexpressed in E. coli strain BL‐21 (DE3).…”

Section: Methodsmentioning

confidence: 99%

Analyzing the role of CagV, a VirB8 homolog of the type IV secretion system of Helicobacter pylori

et al. 2017

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The type IV secretion system of Helicobacter pylori (Cag‐T4 SS ) is composed of ~ 27 components including a VirB8 homolog, CagV. We have characterized CagV and reported that it is an inner membrane protein and, like VirB8, forms a homodimer. Its stability is not dependent on the other Cag components and the absence of cagV affects the stability of only CagI, a protein involved in pilus formation. CagV is not required for the stability and localization of outer membrane subcomplex proteins, but interacts with them through CagX. It also interacts with the inner membrane‐associated components, CagF and CagZ, and is required for the surface localization of CagA. The results of this study might help in deciphering the mechanistic contributions of CagV in the Cag‐T4 SS biogenesis and function.

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“…Cag3 is essential for cag T4SS activity given that cag3 mutant strains are defective in pilus formation, and therefore, are unable to translocate CagA and induce IL‐8 in the human gastric epithelial cell line AGS . cag3 is transcribed, along with cag1 , cag2 , and cag4 (numbered in the direction of transcription).…”

Section: Cag3 (Cagδ/hp0522)mentioning

confidence: 99%

Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS

2017

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The Helicobacter pylori infection of the human gastric mucosa causes chronic active gastritis and peptic ulcers and is associated with the development of gastric cancer. Epidemiological studies show that these gastric diseases are related to virulent H. pylori strains that harbor the cytotoxin‐associated gene pathogenicity island (cag PAI). The cag PAI is a DNA insertion in the H. pylori chromosome that encodes ~ 27 proteins, including the oncoprotein CagA. Approximately 20 of these proteins have been designated as cag type IV secretion system (T4SS) components. However, only 11 of these proteins share function, structure, and/or sequence similarities with the prototypical VirB/VirD4 T4SS of Agrobacterium tumefaciens. The VirB/VirD4 orthologs of the cag T4SS of H. pylori are required for CagA translocation and stimulate the gastric epithelial cells to produce and secrete interleukin‐8 (IL‐8). The cag PAI encodes eight additional proteins, such as Cag3 (Cagδ/HP0522), CagM (Cag16/HP0537), CagU (Cag11/HP0531), CagI (Cag19/HP0540), and CagH (Cag20/HP0541), which are also required for the translocation of CagA and IL‐8 secretion, meanwhile CagF (Cag22/HP0543), CagG (Cag21/HP0542), and CagZ (Cag6/HP0526) are just required for the translocation of CagA. However, relatively little is known about their functions and structural organization because they exhibit a nondetectable sequence similarity with T4SS components in the current databases. In this review, we conducted an exhaustive analysis of the literature to present the biochemistry, putative role, localization, and interactions of each of these eight additional cag T4SS components.

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Cag Type IV Secretion System: CagI Independent Bacterial Surface Localization of CagA

Cited by 24 publications

References 43 publications

Biochemical characterization of the Helicobacter pylori Cag‐type IV secretion system unique component CagU

Biochemical characterization of the Helicobacter pylori Cag‐type IV secretion system unique component CagU

Analyzing the role of CagV, a VirB8 homolog of the type IV secretion system of Helicobacter pylori

Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS

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