DOI: 10.1111/j.1742-4658.2011.08035.x. Role of the <i>cag</i>‐pathogenicity island encoded type IV secretion system in <i>Helicobacter pylori</i> pathogenesis

Role of the cag‐pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis

10.1111/j.1742-4658.2011.08035.x

Crossref journal-article

Wiley

The FEBS Journal (311)

Abstract

Helicobacter pylori is a very successful human‐specific bacterium worldwide. Infections of the stomach with this pathogen can induce pathologies, including chronic gastritis, peptic ulcers and even gastric cancer. Highly virulent H. pylori strains encode the cytotoxin‐associated gene (cag)‐pathogenicity island, which expresses a type IV secretion system (T4SS). This T4SS forms a syringe‐like pilus structure for the injection of virulence factors such as the CagA effector protein into host target cells. This is achieved by a number of T4SS proteins, including CagI, CagL, CagY and CagA, which by itself binds the host cell integrin member β1 followed by delivery of CagA across the host cell membrane. A role of CagA interaction with phosphatidylserine has also been shown to be important for the injection process. After delivery, CagA becomes phosphorylated by oncogenic tyrosine kinases and mimics a host cell factor for the activation or inactivation of some specific intracellular signalling pathways. We review recent progress aiming to characterize the CagA‐dependent and CagA‐independent signalling capabilities of the T4SS, which include the induction of membrane dynamics, disruption of cell–cell junctions and actin‐cytoskeletal rearrangements, as well as pro‐inflammatory, cell cycle‐related and anti‐apoptotic transcriptional responses. The contribution of these signalling pathways to pathogenesis during H. pylori infections is discussed.

Bibliography

Tegtmeyer, N., Wessler, S., & Backert, S. (2011). Role of the cagâpathogenicity island encoded type IV secretion system in Helicobacterâpylori pathogenesis. The FEBS Journal, 278(8), 1190â1202. Portico.

Authors 3

Nicole Tegtmeyer (first)
Silja Wessler (additional)
Steffen Backert (additional)

References 30 Referenced 205

Dates

Type	When
Created	14 years, 7 months ago (Feb. 1, 2011, 9:43 a.m.)
Deposited	1 year, 10 months ago (Oct. 7, 2023, 4:24 a.m.)
Indexed	2 months ago (July 3, 2025, 9:53 a.m.)
Issued	14 years, 6 months ago (Feb. 25, 2011)
Published	14 years, 6 months ago (Feb. 25, 2011)
Published Online	14 years, 6 months ago (Feb. 25, 2011)
Published Print	14 years, 5 months ago (April 1, 2011)

Funders 0

None

BibTeX

@article{Tegtmeyer_2011, title={Role of the cag‐pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis}, volume={278}, ISSN={1742-4658}, url={http://dx.doi.org/10.1111/j.1742-4658.2011.08035.x}, DOI={10.1111/j.1742-4658.2011.08035.x}, number={8}, journal={The FEBS Journal}, publisher={Wiley}, author={Tegtmeyer, Nicole and Wessler, Silja and Backert, Steffen}, year={2011}, month=feb, pages={1190–1202} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        3
      ]
    ],
    "date-time": "2025-07-03T13:53:40Z",
    "timestamp": 1751550820726
  },
  "reference-count": 30,
  "publisher": "Wiley",
  "issue": "8",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2011,
            2,
            25
          ]
        ],
        "date-time": "2011-02-25T00:00:00Z",
        "timestamp": 1298592000000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2011,
        4
      ]
    ]
  },
  "abstract": "<jats:p><jats:italic>Helicobacter\u2003pylori</jats:italic> is a very successful human\u2010specific bacterium worldwide. Infections of the stomach with this pathogen can induce pathologies, including chronic gastritis, peptic ulcers and even gastric cancer. Highly virulent <jats:italic>H.\u2003pylori</jats:italic> strains encode the <jats:italic>cytotoxin\u2010associated gene</jats:italic> (<jats:italic>cag</jats:italic>)\u2010pathogenicity island, which expresses a type IV secretion system (T4SS). This T4SS forms a syringe\u2010like pilus structure for the injection of virulence factors such as the CagA effector protein into host target cells. This is achieved by a number of T4SS proteins, including CagI, CagL, CagY and CagA, which by itself binds the host cell integrin member \u03b2<jats:sub>1</jats:sub> followed by delivery of CagA across the host cell membrane. A role of CagA interaction with phosphatidylserine has also been shown to be important for the injection process. After delivery, CagA becomes phosphorylated by oncogenic tyrosine kinases and mimics a host cell factor for the activation or inactivation of some specific intracellular signalling pathways. We review recent progress aiming to characterize the CagA\u2010dependent and CagA\u2010independent signalling capabilities of the T4SS, which include the induction of membrane dynamics, disruption of cell\u2013cell junctions and actin\u2010cytoskeletal rearrangements, as well as pro\u2010inflammatory, cell cycle\u2010related and anti\u2010apoptotic transcriptional responses. The contribution of these signalling pathways to pathogenesis during <jats:italic>H.\u2003pylori</jats:italic> infections is discussed.</jats:p>",
  "DOI": "10.1111/j.1742-4658.2011.08035.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2011,
        2,
        1
      ]
    ],
    "date-time": "2011-02-01T14:43:27Z",
    "timestamp": 1296571407000
  },
  "page": "1190-1202",
  "source": "Crossref",
  "is-referenced-by-count": 205,
  "title": "Role of the <i>cag</i>\u2010pathogenicity island encoded type IV secretion system in <i>Helicobacter\u2003pylori</i> pathogenesis",
  "prefix": "10.1111",
  "volume": "278",
  "author": [
    {
      "given": "Nicole",
      "family": "Tegtmeyer",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Silja",
      "family": "Wessler",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Steffen",
      "family": "Backert",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2011,
        2,
        25
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_10_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/path.1868"
    },
    {
      "key": "e_1_2_10_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1053/j.gastro.2007.11.009"
    },
    {
      "key": "e_1_2_10_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI38605"
    },
    {
      "key": "e_1_2_10_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.pgen.1001069"
    },
    {
      "key": "e_1_2_10_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ni1131"
    },
    {
      "key": "e_1_2_10_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1462-5822.2008.01156.x"
    },
    {
      "key": "e_1_2_10_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.mib.2007.12.003"
    },
    {
      "key": "e_1_2_10_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/embor.2010.114"
    },
    {
      "key": "e_1_2_10_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.tim.2010.08.003"
    },
    {
      "key": "e_1_2_10_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.2003.03549.x"
    },
    {
      "key": "e_1_2_10_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature06187"
    },
    {
      "key": "e_1_2_10_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JB.01341-07"
    },
    {
      "key": "e_1_2_10_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1000684"
    },
    {
      "key": "e_1_2_10_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.chom.2010.04.005"
    },
    {
      "key": "e_1_2_10_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.tim.2008.05.005"
    },
    {
      "key": "e_1_2_10_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.192.11.1601"
    },
    {
      "key": "e_1_2_10_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1053/j.gastro.2005.02.064"
    },
    {
      "key": "e_1_2_10_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0504927102"
    },
    {
      "key": "e_1_2_10_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0711183105"
    },
    {
      "key": "e_1_2_10_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.2000.02089.x"
    },
    {
      "key": "e_1_2_10_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4161/epi.4.8.10217"
    },
    {
      "key": "e_1_2_10_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm1566"
    },
    {
      "key": "e_1_2_10_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200208039"
    },
    {
      "key": "e_1_2_10_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M107630200"
    },
    {
      "key": "e_1_2_10_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M109.096214"
    },
    {
      "key": "e_1_2_10_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1523-5378.2010.00759.x"
    },
    {
      "key": "e_1_2_10_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.chom.2007.09.005"
    },
    {
      "key": "e_1_2_10_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/onc.2010.304"
    },
    {
      "key": "e_1_2_10_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1086/604727"
    },
    {
      "key": "e_1_2_10_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M801818200"
    }
  ],
  "container-title": "The FEBS Journal",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2011.08035.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2011.08035.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        7
      ]
    ],
    "date-time": "2023-10-07T08:24:41Z",
    "timestamp": 1696667081000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2011.08035.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2011,
        2,
        25
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "8",
    "published-print": {
      "date-parts": [
        [
          2011,
          4
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1111/j.1742-4658.2011.08035.x"
  ],
  "URL": "http://dx.doi.org/10.1111/j.1742-4658.2011.08035.x",
  "relation": {},
  "ISSN": [
    "1742-464X",
    "1742-4658"
  ],
  "subject": [],
  "container-title-short": "The FEBS Journal",
  "published": {
    "date-parts": [
      [
        2011,
        2,
        25
      ]
    ]
  }
}