DOI: 10.1128/aac.00432-10. VraSR Two-Component Regulatory System Contributes to <i>mprF</i> -Mediated Decreased Susceptibility to Daptomycin in <i>In Vivo</i> -Selected Clinical Strains of Methicillin-Resistant Staphylococcus aureus

VraSR Two-Component Regulatory System Contributes to mprF -Mediated Decreased Susceptibility to Daptomycin in In Vivo -Selected Clinical Strains of Methicillin-Resistant Staphylococcus aureus

10.1128/aac.00432-10

Crossref journal-article

American Society for Microbiology

Antimicrobial Agents and Chemotherapy (235)

Abstract

ABSTRACT Daptomycin (DAP) is a new class of cyclic lipopeptide antibiotic highly active against methicillin-resistant Staphylococcus aureus (MRSA) infections. Proposed mechanisms involve disruption of the functional integrity of the bacterial membrane in a Ca-dependent manner. In the present work, we investigated the molecular basis of DAP resistance in a group of isogenic MRSA clinical strains obtained from patients with S. aureus infections after treatment with DAP. Different point mutations were found in the mprF gene in DAP-resistant (DR) strains. Investigation of the mprF L826F mutation in DR strains was accomplished by inactivation and transcomplementation of either full-length wild-type or mutated mprF in DAP-susceptible (DS) strains, revealing that they were mechanistically linked to the DR phenotype. However, our data suggested that mprF was not the only factor determining the resistance to DAP. Differential gene expression analysis showed upregulation of the two-component regulatory system vraSR . Inactivation of vraSR resulted in increased DAP susceptibility, while complementation of vraSR mutant strains restored DAP resistance to levels comparable to those observed in the corresponding DR wild-type strain. Electron microscopy analysis showed a thicker cell wall in DR CB5012 than DS CB5011, an effect that was related to the impact of vraSR and mprF mutations in the cell wall. Moreover, overexpression of vraSR in DS strains resulted in both increased resistance to DAP and decreased resistance to oxacillin, similar to the phenotype observed in DR strains. These results support the suggestion that, in addition to mutations in mprF , vraSR contributes to DAP resistance in the present group of clinical strains.

Bibliography

Mehta, S., Cuirolo, A. X., Plata, K. B., Riosa, S., Silverman, J. A., Rubio, A., Rosato, R. R., & Rosato, A. E. (2012). VraSR Two-Component Regulatory System Contributes to mprF -Mediated Decreased Susceptibility to Daptomycin in In Vivo -Selected Clinical Strains of Methicillin-Resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 56(1), 92â102.

Authors 8

Shrenik Mehta (first)
Arabela X. Cuirolo (additional)
Konrad B. Plata (additional)
Sarah Riosa (additional)
Jared A. Silverman (additional)
Aileen Rubio (additional)
Roberto R. Rosato (additional)
Adriana E. Rosato (additional)

References 49 Referenced 113

10.1086/420818
10.1016/j.cbpa.2009.02.031
10.1039/b416648p
10.1128/jcm.33.3.551-555.1995
10.1128/AAC.01226-10
10.1111/j.1574-6968.2006.00384.x
10.1128/AAC.00417-08
10.1128/AAC.39.2.462
10.1056/NEJMe058023
10.1128/AAC.33.4.424
10.1128/AAC.44.9.2276-2285.2000
10.1093/jac/dkp164
10.1186/1471-2180-11-16
10.1371/journal.ppat.1000660
10.1128/AAC.46.1.24-30.2002
10.1093/jac/dkr195
10.1128/AAC.00039-06
10.1128/AAC.00356-06
10.1128/AAC.00040-07
10.1128/JCM.00519-08
10.1128/AAC.01329-08
IchihashiN KurokawaK MatsuoM KaitoC SekimizuK. 2003. Inhibitory effects of basic or neutral phospholipid on acidic phospholipid-mediated dissociation of adenine nucleotide bound to DnaA protein, the initiator of chromosomal DNA replication. J. Biol. Chem. 278:28778–28786. (10.1074/jbc.M212202200) / J. Biol. Chem / Inhibitory effects of basic or neutral phospholipid on acidic phospholipid-mediated dissociation of adenine nucleotide bound to DnaA protein, the initiator of chromosomal DNA replication by Ichihashi N (2003)
10.1128/AAC.45.5.1323-1336.2001
10.1128/AAC.01704-10
10.1128/AAC.00719-07
10.1128/AAC.00559-07
10.1073/pnas.0710217105
10.1046/j.1365-2958.2003.03599.x
10.1016/S0140-6736(00)04403-2
10.1006/meth.2001.1262
10.1128/AAC.44.7.1825-1831.2000
10.1128/AAC.01682-08
MoePC LevinG BlountP. 2000. Correlating a protein structure with function of a bacterial mechanosensitive channel. J. Biol. Chem. 275:31121–31127. (10.1074/jbc.M002971200) / J. Biol. Chem / Correlating a protein structure with function of a bacterial mechanosensitive channel by Moe PC (2000)
10.1128/JB.187.7.2357-2367.2005
10.1128/AAC.01121-07
NCCLS/CLSI. 2007. Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-A8, 8th ed. NCCLS/CLSI, Wayne, PA. / Approved standard M2-A8 by NCCLS/CLSI (2007)
10.1016/0042-6822(67)90105-5
10.1128/AAC.46.7.2155-2161.2002
10.1016/j.ijantimicag.2011.06.010
10.1084/jem.193.9.1067
10.1074/jbc.274.13.8405
10.1128/AAC.00202-07
10.1099/jmm.0.05176-0
10.1128/JB.185.11.3446-3452.2003
10.1128/JCM.33.9.2233-2239.1995
YangSJ. 2009. Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus. J. Infect. Dis. 200:1916–1920. (10.1086/648473) / Infect. Dis / Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus by Yang SJ (2009)
10.1128/AAC.00487-10
10.1128/AAC.01415-08
10.1128/AAC.50.1.336-343.2006

Dates

Type	When
Created	13 years, 10 months ago (Oct. 11, 2011, 1:29 a.m.)
Deposited	3 years, 6 months ago (Feb. 21, 2022, 5:24 p.m.)
Indexed	1 month, 1 week ago (July 20, 2025, 12:10 a.m.)
Issued	13 years, 8 months ago (Jan. 1, 2012)
Published	13 years, 8 months ago (Jan. 1, 2012)
Published Print	13 years, 8 months ago (Jan. 1, 2012)

Funders 0

None

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        20
      ]
    ],
    "date-time": "2025-07-20T04:10:51Z",
    "timestamp": 1752984651253
  },
  "reference-count": 49,
  "publisher": "American Society for Microbiology",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2012,
            1,
            1
          ]
        ],
        "date-time": "2012-01-01T00:00:00Z",
        "timestamp": 1325376000000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2012,
        1
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Daptomycin (DAP) is a new class of cyclic lipopeptide antibiotic highly active against methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus</jats:named-content>\n            (MRSA) infections. Proposed mechanisms involve disruption of the functional integrity of the bacterial membrane in a Ca-dependent manner. In the present work, we investigated the molecular basis of DAP resistance in a group of isogenic MRSA clinical strains obtained from patients with\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus</jats:named-content>\n            infections after treatment with DAP. Different point mutations were found in the\n            <jats:italic>mprF</jats:italic>\n            gene in DAP-resistant (DR) strains. Investigation of the\n            <jats:italic>mprF</jats:italic>\n            L826F mutation in DR strains was accomplished by inactivation and transcomplementation of either full-length wild-type or mutated\n            <jats:italic>mprF</jats:italic>\n            in DAP-susceptible (DS) strains, revealing that they were mechanistically linked to the DR phenotype. However, our data suggested that\n            <jats:italic>mprF</jats:italic>\n            was not the only factor determining the resistance to DAP. Differential gene expression analysis showed upregulation of the two-component regulatory system\n            <jats:italic>vraSR</jats:italic>\n            . Inactivation of\n            <jats:italic>vraSR</jats:italic>\n            resulted in increased DAP susceptibility, while complementation of\n            <jats:italic>vraSR</jats:italic>\n            mutant strains restored DAP resistance to levels comparable to those observed in the corresponding DR wild-type strain. Electron microscopy analysis showed a thicker cell wall in DR CB5012 than DS CB5011, an effect that was related to the impact of\n            <jats:italic>vraSR</jats:italic>\n            and\n            <jats:italic>mprF</jats:italic>\n            mutations in the cell wall. Moreover, overexpression of\n            <jats:italic>vraSR</jats:italic>\n            in DS strains resulted in both increased resistance to DAP and decreased resistance to oxacillin, similar to the phenotype observed in DR strains. These results support the suggestion that, in addition to mutations in\n            <jats:italic>mprF</jats:italic>\n            ,\n            <jats:italic>vraSR</jats:italic>\n            contributes to DAP resistance in the present group of clinical strains.\n          </jats:p>",
  "DOI": "10.1128/aac.00432-10",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2011,
        10,
        11
      ]
    ],
    "date-time": "2011-10-11T05:29:43Z",
    "timestamp": 1318310983000
  },
  "page": "92-102",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 113,
  "title": "VraSR Two-Component Regulatory System Contributes to\n            <i>mprF</i>\n            -Mediated Decreased Susceptibility to Daptomycin in\n            <i>In Vivo</i>\n            -Selected Clinical Strains of Methicillin-Resistant Staphylococcus aureus",
  "prefix": "10.1128",
  "volume": "56",
  "author": [
    {
      "given": "Shrenik",
      "family": "Mehta",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA"
        }
      ]
    },
    {
      "given": "Arabela X.",
      "family": "Cuirolo",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA"
        }
      ]
    },
    {
      "given": "Konrad B.",
      "family": "Plata",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"
        }
      ]
    },
    {
      "given": "Sarah",
      "family": "Riosa",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"
        }
      ]
    },
    {
      "given": "Jared A.",
      "family": "Silverman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cubist Pharmaceuticals, Lexington, Massachusetts, USA"
        }
      ]
    },
    {
      "given": "Aileen",
      "family": "Rubio",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cubist Pharmaceuticals, Lexington, Massachusetts, USA"
        }
      ]
    },
    {
      "given": "Roberto R.",
      "family": "Rosato",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"
        }
      ]
    },
    {
      "given": "Adriana E.",
      "family": "Rosato",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1086/420818"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cbpa.2009.02.031"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1039/b416648p"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jcm.33.3.551-555.1995"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01226-10"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1574-6968.2006.00384.x"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00417-08"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.39.2.462"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJMe058023"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.33.4.424"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.44.9.2276-2285.2000"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jac/dkp164"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/1471-2180-11-16"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1000660"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.46.1.24-30.2002"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jac/dkr195"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00039-06"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00356-06"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00040-07"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JCM.00519-08"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01329-08"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "crossref",
      "first-page": "28778",
      "DOI": "10.1074/jbc.M212202200",
      "article-title": "Inhibitory effects of basic or neutral phospholipid on acidic phospholipid-mediated dissociation of adenine nucleotide bound to DnaA protein, the initiator of chromosomal DNA replication",
      "volume": "278",
      "author": "Ichihashi N",
      "year": "2003",
      "unstructured": "IchihashiN KurokawaK MatsuoM KaitoC SekimizuK. 2003. Inhibitory effects of basic or neutral phospholipid on acidic phospholipid-mediated dissociation of adenine nucleotide bound to DnaA protein, the initiator of chromosomal DNA replication. J. Biol. Chem. 278:28778\u201328786.",
      "journal-title": "J. Biol. Chem"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.45.5.1323-1336.2001"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01704-10"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00719-07"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00559-07"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0710217105"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.2003.03599.x"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0140-6736(00)04403-2"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/meth.2001.1262"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.44.7.1825-1831.2000"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01682-08"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "crossref",
      "first-page": "31121",
      "DOI": "10.1074/jbc.M002971200",
      "article-title": "Correlating a protein structure with function of a bacterial mechanosensitive channel",
      "volume": "275",
      "author": "Moe PC",
      "year": "2000",
      "unstructured": "MoePC LevinG BlountP. 2000. Correlating a protein structure with function of a bacterial mechanosensitive channel. J. Biol. Chem. 275:31121\u201331127.",
      "journal-title": "J. Biol. Chem"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JB.187.7.2357-2367.2005"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01121-07"
    },
    {
      "key": "e_1_3_2_37_2",
      "volume-title": "Approved standard M2-A8",
      "author": "NCCLS/CLSI",
      "year": "2007",
      "unstructured": "NCCLS/CLSI. 2007. Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-A8, 8th ed. NCCLS/CLSI, Wayne, PA.",
      "edition": "8"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(67)90105-5"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.46.7.2155-2161.2002"
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.ijantimicag.2011.06.010"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.193.9.1067"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.13.8405"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00202-07"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/jmm.0.05176-0"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JB.185.11.3446-3452.2003"
    },
    {
      "key": "e_1_3_2_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JCM.33.9.2233-2239.1995"
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "crossref",
      "first-page": "1916",
      "DOI": "10.1086/648473",
      "article-title": "Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus",
      "volume": "200",
      "author": "Yang SJ",
      "year": "2009",
      "unstructured": "YangSJ. 2009. Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus. J. Infect. Dis. 200:1916\u20131920.",
      "journal-title": "Infect. Dis"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.00487-10"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.01415-08"
    },
    {
      "key": "e_1_3_2_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.50.1.336-343.2006"
    }
  ],
  "container-title": "Antimicrobial Agents and Chemotherapy",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/AAC.00432-10",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/AAC.00432-10",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        2,
        21
      ]
    ],
    "date-time": "2022-02-21T22:24:49Z",
    "timestamp": 1645482289000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/AAC.00432-10"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2012,
        1
      ]
    ]
  },
  "references-count": 49,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          2012,
          1
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/AAC.00432-10"
  ],
  "URL": "http://dx.doi.org/10.1128/AAC.00432-10",
  "relation": {},
  "ISSN": [
    "0066-4804",
    "1098-6596"
  ],
  "subject": [],
  "container-title-short": "Antimicrob Agents Chemother",
  "published": {
    "date-parts": [
      [
        2012,
        1
      ]
    ]
  },
  "assertion": [
    {
      "value": "2010-03-31",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2011-09-27",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2012-12-26",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}