DOI: 10.1073/pnas.0406873102. <i>Brucella</i> coopts the small GTPase Sar1 for intracellular replication

Brucella coopts the small GTPase Sar1 for intracellular replication

10.1073/pnas.0406873102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The pathogen Brucella abortus resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the Brucella type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investigated a putative role of the early secretory pathway in ER membrane accretion by the Brucella -containing vacuoles (BCVs). We show that BCVs interact with ER exit sites (ERES), and blockade of Sar1 activity, which disrupts ERES, prevents intracellular replication of Brucella . In cells expressing the dominant interfering form Sar1[T39N], BCVs do not acquire ER membranes, suggesting that they are unable to mature into replicative organelles. By contrast, treatments that block subsequent secretory events do not affect bacterial replication. We propose that Sar1-dependent ERES functions, but not subsequent secretory events, are essential for the biogenesis of the Brucella replicative compartment and, thus, bacterial replication. These results assign an essential role for Sar1 in pathogenesis of an intracellular bacterium.

Bibliography

Celli, J., Salcedo, S. P., & Gorvel, J.-P. (2005). Brucella coopts the small GTPase Sar1 for intracellular replication. Proceedings of the National Academy of Sciences, 102(5), 1673â1678.

Authors 3

Jean Celli (first)
Suzana P. Salcedo (additional)
Jean-Pierre Gorvel (additional)

References 25 Referenced 147

10.1084/jem.20030088
10.1046/j.1365-2958.1999.01569.x
10.1128/IAI.66.12.5711-5724.1998
10.1046/j.1462-5822.2001.00102.x
10.1016/S0092-8674(00)80379-7
10.1242/jcs.113.12.2177
10.1016/0092-8674(94)90138-4
10.1016/S0955-0674(02)00348-4
10.1083/jcb.131.4.875
10.1083/jcb.200107045
10.1016/0378-1119(91)90599-7
10.1046/j.1462-5822.2001.00131.x
Kovach, M. E., Phillips, R. W., Elzer, P. H., Roop, R. M., II, & Peterson, K. M. (1994) BioTechniques 16, 800–802.8068328 / BioTechniques (1994)
10.1128/jvi.70.8.5701-5705.1996
10.1083/jcb.128.6.1003
10.1128/iai.61.9.3775-3784.1993
10.1046/j.1462-5822.2002.00221.x
10.1242/jcs.112.24.4547
10.1046/j.1462-5822.1999.00003.x
10.1083/jcb.107.5.1643
10.1046/j.1365-2958.2000.02176.x
10.1074/jbc.271.8.4031
10.1038/ncb883
10.1038/34438
10.1034/j.1600-0854.2002.31108.x

Dates

Type	When
Created	20 years, 7 months ago (Jan. 4, 2005, 9:33 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:21 a.m.)
Indexed	1 month, 3 weeks ago (July 8, 2025, 1:45 a.m.)
Issued	20 years, 7 months ago (Jan. 4, 2005)
Published	20 years, 7 months ago (Jan. 4, 2005)
Published Online	20 years, 7 months ago (Jan. 4, 2005)
Published Print	20 years, 7 months ago (Feb. 1, 2005)

Funders 0

None

BibTeX

@article{Celli_2005, title={Brucella coopts the small GTPase Sar1 for intracellular replication}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0406873102}, DOI={10.1073/pnas.0406873102}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Celli, Jean and Salcedo, Suzana P. and Gorvel, Jean-Pierre}, year={2005}, month=jan, pages={1673–1678} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        8
      ]
    ],
    "date-time": "2025-07-08T05:45:30Z",
    "timestamp": 1751953530991
  },
  "reference-count": 25,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "5",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        2
      ]
    ]
  },
  "abstract": "<jats:p>\n            The pathogen\n            <jats:italic>Brucella abortus</jats:italic>\n            resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the\n            <jats:italic>Brucella</jats:italic>\n            type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investigated a putative role of the early secretory pathway in ER membrane accretion by the\n            <jats:italic>Brucella</jats:italic>\n            -containing vacuoles (BCVs). We show that BCVs interact with ER exit sites (ERES), and blockade of Sar1 activity, which disrupts ERES, prevents intracellular replication of\n            <jats:italic>Brucella</jats:italic>\n            . In cells expressing the dominant interfering form Sar1[T39N], BCVs do not acquire ER membranes, suggesting that they are unable to mature into replicative organelles. By contrast, treatments that block subsequent secretory events do not affect bacterial replication. We propose that Sar1-dependent ERES functions, but not subsequent secretory events, are essential for the biogenesis of the\n            <jats:italic>Brucella</jats:italic>\n            replicative compartment and, thus, bacterial replication. These results assign an essential role for Sar1 in pathogenesis of an intracellular bacterium.\n          </jats:p>",
  "DOI": "10.1073/pnas.0406873102",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        1,
        5
      ]
    ],
    "date-time": "2005-01-05T02:33:11Z",
    "timestamp": 1104892391000
  },
  "page": "1673-1678",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 147,
  "title": "<i>Brucella</i>\n            coopts the small GTPase Sar1 for intracellular replication",
  "prefix": "10.1073",
  "volume": "102",
  "author": [
    {
      "given": "Jean",
      "family": "Celli",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Centre d'Immunologie de Marseille-Luminy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale/Centre National de la Recherche Scientifique/Universit\u00e9 delaM\u00e9diterran\u00e9e, Parc Scientifique et Technologique de Luminy, Case 906, 13288 Marseille Cedex 09, France"
        }
      ]
    },
    {
      "given": "Suzana P.",
      "family": "Salcedo",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Centre d'Immunologie de Marseille-Luminy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale/Centre National de la Recherche Scientifique/Universit\u00e9 delaM\u00e9diterran\u00e9e, Parc Scientifique et Technologique de Luminy, Case 906, 13288 Marseille Cedex 09, France"
        }
      ]
    },
    {
      "given": "Jean-Pierre",
      "family": "Gorvel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Centre d'Immunologie de Marseille-Luminy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale/Centre National de la Recherche Scientifique/Universit\u00e9 delaM\u00e9diterran\u00e9e, Parc Scientifique et Technologique de Luminy, Case 906, 13288 Marseille Cedex 09, France"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2005,
        1,
        4
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.20030088"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.1999.01569.x"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.66.12.5711-5724.1998"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1462-5822.2001.00102.x"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80379-7"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.113.12.2177"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(94)90138-4"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0955-0674(02)00348-4"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.131.4.875"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200107045"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0378-1119(91)90599-7"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1462-5822.2001.00131.x"
    },
    {
      "key": "e_1_3_2_13_2",
      "first-page": "800",
      "volume": "16",
      "year": "1994",
      "unstructured": "Kovach, M. E., Phillips, R. W., Elzer, P. H., Roop, R. M., II, & Peterson, K. M. (1994) BioTechniques 16, 800\u2013802.8068328",
      "journal-title": "BioTechniques"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.70.8.5701-5705.1996"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.128.6.1003"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.61.9.3775-3784.1993"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1462-5822.2002.00221.x"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.112.24.4547"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1462-5822.1999.00003.x"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.107.5.1643"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.2000.02176.x"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.8.4031"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ncb883"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/34438"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-0854.2002.31108.x"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0406873102",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T12:21:08Z",
    "timestamp": 1649766068000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0406873102"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        1,
        4
      ]
    ]
  },
  "references-count": 25,
  "journal-issue": {
    "issue": "5",
    "published-print": {
      "date-parts": [
        [
          2005,
          2
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0406873102"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0406873102",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1023246.290769",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.3410/f.1023246.266718",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2005,
        1,
        4
      ]
    ]
  },
  "assertion": [
    {
      "value": "2004-09-15",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2005-01-04",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}