{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:06:41Z","timestamp":1792721201569,"version":"4.5.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T00:00:00Z","timestamp":1359417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"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":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>\n                    is an intracellular pathogen that replicates within a lysosome-like vacuole. A Dot\/Icm type IVB secretion system is used by\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    to translocate effector proteins into the host cytosol that likely modulate host factor function. To identify host determinants required for\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    intracellular growth, a genome-wide screen was performed using gene silencing by small interfering RNA (siRNA). Replication of\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    was measured by immunofluorescence microscopy in siRNA-transfected HeLa cells. Newly identified host factors included components of the retromer complex, which mediates cargo cycling between the endocytic pathway and the Golgi apparatus. Reducing the levels of the retromer cargo-adapter VPS26-VPS29-VPS35 complex or retromer-associated sorting nexins abrogated\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    replication. Several genes, when silenced, resulted in enlarged vacuoles or an increased number of vacuoles within\n                    <jats:italic>C.\u00a0burnetii-<\/jats:italic>\n                    infected cells. Silencing of the\n                    <jats:italic>STX17<\/jats:italic>\n                    gene encoding syntaxin-17 resulted in a striking defect in homotypic fusion of vacuoles containing\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    , suggesting a role for syntaxin-17 in regulating this process. Lastly, silencing host genes needed for\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    replication correlated with defects in the translocation of Dot\/Icm effectors, whereas, silencing of genes that affected vacuole morphology, but did not impact replication, did not affect Dot\/Icm translocation. These data demonstrate that\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    vacuole maturation is important for creating a niche that permits Dot\/Icm function. Thus, genome-wide screening has revealed host determinants involved in sequential events that occur during\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    infection as defined by bacterial uptake, vacuole transport and acidification, activation of the Dot\/Icm system, homotypic fusion of vacuoles, and intracellular replication.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Q fever in humans is caused by the bacterium\n                    <jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>\n                    . Infection with\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    is marked by its unique ability to replicate within a large vacuolar compartment inside cells that resembles the harsh, acidic environment of a lysosome. Central to its pathogenesis is the delivery of bacterial effector proteins into the host cell cytosol by a Dot\/Icm type IVB secretion system. These proteins can interact with and manipulate host factors, thereby leading to creation and maintenance of the vacuole that the bacteria grow within. Using high-throughput genome-wide screening in human cells, we identified host factors important for several facets of\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    infection, including vacuole transport and membrane fusion events that promote vacuole expansion. In addition, we show that maturation of the\n                    <jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>\n                    vacuole is necessary for creating an environment permissive for the Dot\/Icm delivery of bacterial effector proteins into the host cytosol.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00606-12","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T23:48:52Z","timestamp":1359503332000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":113,"title":["Host Pathways Important for Coxiella burnetii Infection Revealed by Genome-Wide RNA Interference Screening"],"prefix":"10.1128","volume":"4","author":[{"given":"Justin A.","family":"McDonough","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut, 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