{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:56:38Z","timestamp":1791305798042,"version":"4.3.1"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2011,8,23]],"date-time":"2011-08-23T00:00:00Z","timestamp":1314057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":["mBio"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Central to Q fever pathogenesis is replication of the causative agent,\n                    <jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>\n                    , within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes.\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot\/Icm type IVB secretion system (T4BSS). In this study, we utilized a\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    strain carrying IcmD inactivated by the\n                    <jats:italic>Himar1<\/jats:italic>\n                    transposon to investigate the requirements for Dot\/Icm function in\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    parasitism of human THP-1 macrophage-like cells. The\n                    <jats:italic>icmD<\/jats:italic>\n                    ::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the\n                    <jats:italic>icmD<\/jats:italic>\n                    ::Tn mutant required complementation with\n                    <jats:italic>icmD<\/jats:italic>\n                    ,\n                    <jats:italic>-J<\/jats:italic>\n                    , and\n                    <jats:italic>-B<\/jats:italic>\n                    , indicating a polar effect of the transposon insertion on downstream\n                    <jats:italic>dot<\/jats:italic>\n                    \/\n                    <jats:italic>icm<\/jats:italic>\n                    genes. Induction of\n                    <jats:italic>icmDJB<\/jats:italic>\n                    expression at 1\u00a0day postinfection resulted in\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    . However, illustrating the metabolic flexibility of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>burnetti<\/jats:italic>\n                    , the\n                    <jats:italic>icmD<\/jats:italic>\n                    ::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot\/Icm function is provided in\n                    <jats:italic>trans<\/jats:italic>\n                    , and within a phenotypically similar PV generated by the protozoan parasite\n                    <jats:named-content content-type=\"genus-species\">Leishmania amazonensis<\/jats:named-content>\n                    , where host cells are devoid of Dot\/Icm T4BSS effector proteins.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>\n                    , the cause of human Q fever, is the only bacterial pathogen known to replicate in a vacuole resembling a phagolysosome. The organism manipulates host macrophages to promote the biogenesis of a vacuolar compartment permissive for growth. By analogy to the well-established cellular microbiology of\n                    <jats:named-content content-type=\"genus-species\">Legionella pneumophila<\/jats:named-content>\n                    , the Dot\/Icm type IVB secretion system of\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    is implicated as a critical virulence factor in host cell modification that delivers proteins with effector functions directly into the host cell cytosol. Using new genetic tools, we verify that Dot\/Icm function is essential for productive infection of human macrophages by\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    . Interestingly, despite the production of homologous secretion systems,\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    have strikingly different temporal requirements for Dot\/Icm function during their respective infectious cycles.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00175-11","type":"journal-article","created":{"date-parts":[[2011,8,23]],"date-time":"2011-08-23T20:37:40Z","timestamp":1314131860000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":249,"title":["Dot\/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages"],"prefix":"10.1128","volume":"2","author":[{"given":"Paul A.","family":"Beare","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":"Stacey D.","family":"Gilk","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":"Charles L.","family":"Larson","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":"Joshua","family":"Hill","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":"Christopher M.","family":"Stead","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":"Anders","family":"Omsland","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 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