{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:06:38Z","timestamp":1792721198921,"version":"4.5.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,17]]},"abstract":"<jats:p>\n                    The inability to propagate obligate intracellular pathogens under axenic (host cell-free) culture conditions imposes severe experimental constraints that have negatively impacted progress in understanding pathogen virulence and disease mechanisms.\n                    <jats:italic>Coxiella burnetii<\/jats:italic>\n                    , the causative agent of human Q (Query) fever, is an obligate intracellular bacterial pathogen that replicates exclusively in an acidified, lysosome-like vacuole. To define conditions that support\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    growth, we systematically evaluated the organism's metabolic requirements using expression microarrays, genomic reconstruction, and metabolite typing. This led to development of a complex nutrient medium that supported substantial growth (approximately 3 log\n                    <jats:sub>10<\/jats:sub>\n                    ) of\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    in a 2.5% oxygen environment. Importantly, axenically grown\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    were highly infectious for Vero cells and exhibited developmental forms characteristic of in vivo grown organisms. Axenic cultivation of\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    will facilitate studies of the organism's pathogenesis and genetics and aid development of Q fever preventatives such as an effective subunit vaccine. Furthermore, the systematic approach used here may be broadly applicable to development of axenic media that support growth of other medically important obligate intracellular pathogens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0812074106","type":"journal-article","created":{"date-parts":[[2009,2,25]],"date-time":"2009-02-25T22:19:05Z","timestamp":1235600345000},"page":"4430-4434","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":392,"title":["Host cell-free growth of the Q fever bacterium\n                    <i>Coxiella burnetii<\/i>"],"prefix":"10.1073","volume":"106","author":[{"given":"Anders","family":"Omsland","sequence":"first","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane C.","family":"Cockrell","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Howe","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"Virtaneva","sequence":"additional","affiliation":[{"name":"Genomics Unit, Research Technology Section, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Sturdevant","sequence":"additional","affiliation":[{"name":"Genomics Unit, Research Technology Section, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Porcella","sequence":"additional","affiliation":[{"name":"Genomics Unit, Research Technology Section, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Heinzen","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.4.518"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1937.tb43743.x"},{"key":"e_1_3_3_3_2","first-page":"2270","article-title":"A filter-passing infectious agent isolated from ticks. 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