{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:47:55Z","timestamp":1790095675173,"version":"4.0.1"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"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},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The intracellular bacterial pathogen\n            <jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>\n            directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            replication requires a Dot\/Icm type 4B secretion system (T4BSS) that delivers bacterial effector proteins into the host cell cytosol. Thus, a subset of T4BSS effectors are presumed to direct PV biogenesis. Recently, the PV-localized effector protein CvpA was found to promote\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            intracellular growth and PV expansion. We predict additional\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            effectors localize to the PV membrane and regulate eukaryotic vesicle trafficking events that promote pathogen growth. To identify these vacuolar effector proteins, a list of predicted\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            T4BSS substrates was compiled using bioinformatic criteria, such as the presence of eukaryote-like coiled-coil domains. Adenylate cyclase translocation assays revealed 13 proteins were secreted in a Dot\/Icm-dependent fashion by\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            during infection of human THP-1 macrophages. Four of the Dot\/Icm substrates, termed\n            <jats:named-content content-type=\"genus-species\">\n              <jats:underline>C<\/jats:underline>\n              oxiella\n            <\/jats:named-content>\n            <jats:underline>v<\/jats:underline>\n            acuolar\n            <jats:underline>p<\/jats:underline>\n            rotein B (CvpB), CvpC, CvpD, and CvpE, labeled the PV membrane and LAMP1-positive vesicles when ectopically expressed as fluorescently tagged fusion proteins.\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            \u0394\n            <jats:italic>cvpB<\/jats:italic>\n            , \u0394\n            <jats:italic>cvpC<\/jats:italic>\n            , \u0394\n            <jats:italic>cvpD<\/jats:italic>\n            , and \u0394\n            <jats:italic>cvpE<\/jats:italic>\n            mutants exhibited significant defects in intracellular replication and PV formation. Genetic complementation of the \u0394\n            <jats:italic>cvpD<\/jats:italic>\n            and \u0394\n            <jats:italic>cvpE<\/jats:italic>\n            mutants rescued intracellular growth and PV generation, whereas the growth of\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            \u0394\n            <jats:italic>cvpB<\/jats:italic>\n            and \u0394\n            <jats:italic>cvpC<\/jats:italic>\n            was rescued upon cohabitation with wild-type bacteria in a common PV. Collectively, these data indicate\n            <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n            encodes multiple effector proteins that target the PV membrane and benefit pathogen replication in human macrophages.\n          <\/jats:p>","DOI":"10.1128\/iai.02763-14","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T04:04:41Z","timestamp":1416888281000},"page":"661-670","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["Coxiella burnetii Effector Proteins That Localize to the Parasitophorous Vacuole Membrane Promote Intracellular Replication"],"prefix":"10.1128","volume":"83","author":[{"given":"Charles L.","family":"Larson","sequence":"first","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Beare","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Voth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Howe","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane C.","family":"Cockrell","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Bastidas","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael H.","family":"Valdivia","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Heinzen","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.4.518"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.21.7344-7352.2004"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(99)01475-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.147.3.1063-1076.1981"},{"key":"e_1_3_3_6_2","first-page":"267","volume-title":"Rickettsiae and rickettsial diseases","author":"McCaul TF","year":"1981","unstructured":"McCaul TF, Hackstadt T, Williams JC. 1981. 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