{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:17:47Z","timestamp":1768558667344,"version":"3.49.0"},"reference-count":87,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI00946\u201018"],"award-info":[{"award-number":["AI00946\u201018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Coxiella burnetii<\/jats:italic> is the causative agent of Q fever. All <jats:italic>C. burnetii<\/jats:italic> isolates encode either an autonomously replicating plasmid (QpH1, QpDG, QpRS, or QpDV) or QpRS\u2010like chromosomally integrated plasmid sequences. The role of the ORFs present in these sequences is unknown. Here, the role of the ORFs encoded on QpH1 was investigated. Using a new <jats:italic>C. burnetii<\/jats:italic> shuttle vector (pB\u2010TyrB\u2010QpH1ori), we cured the <jats:italic>C. burnetii<\/jats:italic> Nine Mile Phase II strain of QpH1. The \u0394QpH1 strain grew normally in axenic media but had a significant growth defect in Vero cells, indicating QpH1 was important for <jats:italic>C. burnetii<\/jats:italic> virulence. We developed an inducible CRISPR interference system to examine the role of individual QpH1 plasmid genes. CRISPRi of <jats:italic>cbuA0027<\/jats:italic> resulted in significant growth defects in axenic media and THP\u20101 cells. The <jats:italic>cbuA0028<\/jats:italic>\/<jats:italic>cbuA0027<\/jats:italic> operon encodes CBUA0028 (ToxP) and CBUA0027 (AntitoxP), which are homologous to the HigB2 toxin and HigA2 antitoxin, respectively, from <jats:italic>Vibrio cholerae<\/jats:italic>. Consistent with toxin\u2013antitoxin systems, overexpression of <jats:italic>toxP<\/jats:italic> resulted in a severe intracellular growth defect that was rescued by co\u2010expression of <jats:italic>antitoxP<\/jats:italic>. ToxP inhibited protein translation. AntitoxP bound the <jats:italic>toxP<\/jats:italic> promoter (P<jats:italic>toxP<\/jats:italic>) and ToxP, with the resulting complex binding also P<jats:italic>toxP<\/jats:italic>. In summary, our data indicate that <jats:italic>C. burnetii<\/jats:italic> maintains an autonomously replicating plasmid because of a plasmid\u2010based toxin\u2013antitoxin system.<\/jats:p>","DOI":"10.1111\/mmi.15001","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T07:46:01Z","timestamp":1668671161000},"page":"744-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The endogenous <i>Coxiella burnetii<\/i> plasmid encodes a functional toxin\u2013antitoxin system"],"prefix":"10.1111","volume":"118","author":[{"given":"Shaun","family":"Wachter","sequence":"first","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health  Hamilton Montana USA"},{"name":"Vaccine and Infectious Disease Organization  Saskatoon Saskatchewan Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane C.","family":"Cockrell","sequence":"additional","affiliation":[{"name":"Vector\u2010Pathogen\u2010Host Interaction unit, Laboratory of Bacteriology, Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health  Hamilton Montana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Cytek Biosciences  Fremont California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimmo","family":"Virtaneva","sequence":"additional","affiliation":[{"name":"Genomics Research Section, Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health  Hamilton Montana 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-177X","authenticated-orcid":false,"given":"Paul A.","family":"Beare","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health  Hamilton Montana USA"},{"name":"Genomics Research Section, Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health  Hamilton Montana 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