{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:20:45Z","timestamp":1788931245389,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Coxiella burnetii<\/jats:italic> is the etiological agent of Q fever, a worldwide zoonosis able to cause large outbreaks. The disease is polymorphic. Symptomatic primary infection is named acute Q fever and is associated with hepatitis, pneumonia, fever, and auto-immune complications while persistent focalized infections, mainly endocarditis, and vascular infections, occur in a minority of patients but are potentially lethal. In order to evaluate the genomic features, genetic diversity, evolution, as well as genetic determinants of antibiotic resistance, pathogenicity, and ability to cause outbreaks of Q fever, we performed a pangenomic analysis and genomic comparison of 75 <jats:italic>C. burnetii<\/jats:italic> strains including 63 newly sequenced genomes. Our analysis demonstrated that <jats:italic>C. burnetii<\/jats:italic> has an open pangenome, unique genes being found in many strains. In addition, pathogenicity islands were detected in all genomes. In consequence <jats:italic>C. burnetii<\/jats:italic> has a high genomic plasticity, higher than that of other intracellular bacteria. The core- and pan-genomes are made of 1,211 and 4,501 genes, respectively (ratio 0.27). The core gene-based phylogenetic analysis matched that obtained from multi-spacer typing and the distribution of plasmid types. Genomic characteristics were associated to clinical and epidemiological features. Some genotypes were associated to specific clinical forms and countries. MST1 genotype strains were associated to acute Q fever. A significant association was also found between clinical forms and plasmids. Strains harboring the QpRS plasmid were never found in acute Q fever and were only associated to persistent focalized infections. The QpDV and QpH1 plasmids were associated to acute Q fever. In addition, the Guyanese strain CB175, the most virulent strain to date, exhibited a unique MST genotype, a distinct COG profile and an important variation in gene number that may explain its unique pathogenesis. Therefore, strain-specific factors play an important role in determining the epidemiological and clinical manifestations of Q fever alongside with host-specific factors (valvular and vascular defects notably).<\/jats:p>","DOI":"10.3389\/fmicb.2022.1022356","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T18:42:27Z","timestamp":1669056147000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Pangenomic analysis of Coxiella burnetii unveils new traits in genome architecture"],"prefix":"10.3389","volume":"13","author":[{"given":"Rita","family":"Abou Abdallah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Million","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Delerce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Anani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awa","family":"Diop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Caputo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Zgheib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Rousset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Sidi Boumedine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Raoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Edouard","family":"Fournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.vetmic.2009.07.016","article-title":"Q fever.","volume":"140","author":"Angelakis","year":"2010","journal-title":"Vet. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1128\/JCM.03371-13","article-title":"Emergence of Q fever arthritis in France.","volume":"52","author":"Angelakis","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s10096-012-1750-3","article-title":"Q fever and pregnancy: Disease, prevention, and strain specificity.","volume":"32","author":"Angelakis","year":"2013","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001540","article-title":"Comparison of real-time quantitative PCR and culture for the diagnosis of emerging rickettsioses.","volume":"6","author":"Angelakis","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4056\/sigs.531120","article-title":"Digital DNA-DNA hybridization for microbial species delineation by means of genome-to-genome sequence comparison.","volume":"2","author":"Auch","year":"2010","journal-title":"Stand. Genom. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes - A new genome assembly algorithm and its applications to single-cell sequencing.","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1128\/IAI.01141-08","article-title":"Comparative genomics reveal extensive transposon-mediated genomic plasticity and diversity among potential effector proteins within the genus Coxiella.","volume":"77","author":"Beare","year":"2009","journal-title":"Infect. Immun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"W30","DOI":"10.1093\/nar\/gkx343","article-title":"IslandViewer 4: Expanded prediction of genomic islands for larger-scale datasets.","volume":"45","author":"Bertelli","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1378\/chest.114.3.808","article-title":"Acute Q fever pneumonia: A review of 80 hospitalized patients.","volume":"114","author":"Caron","year":"1998","journal-title":"Chest"},{"key":"B10","doi-asserted-by":"publisher","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: A reference database for bacterial virulence factors.","volume":"33","author":"Chen","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"253","DOI":"10.2217\/fmb.15.137","article-title":"The contribution of genomics to the study of Q fever.","volume":"11","author":"D\u2019Amato","year":"2016","journal-title":"Future Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cimid.2015.04.003","article-title":"Loss of TSS1 in hypervirulent Coxiella burnetii 175, the causative agent of Q fever in French Guiana.","volume":"41","author":"D\u2019Amato","year":"2015","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cimid.2014.08.003","article-title":"The genome of Coxiella burnetii Z3055, a clone linked to the Netherlands Q fever outbreaks, provides evidence for the role of drift in the emergence of epidemic clones.","volume":"37","author":"D\u2019Amato","year":"2014","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1746-6148-8-165","article-title":"Molecular typing of Coxiella burnetii from animal and environmental matrices during Q fever epidemics in the Netherlands.","volume":"8","author":"de Bruin","year":"2012","journal-title":"BMC Vet. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1093\/clinids\/5.4.790","article-title":"\u201cQ\u201d fever, a new fever entity: Clinical features, diagnosis and laboratory investigation.","volume":"5","author":"Derrick","year":"1983","journal-title":"Clin. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1128\/CMR.00045-16","article-title":"From Q fever to Coxiella burnetii infection: A paradigm change.","volume":"30","author":"Eldin","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1086\/320159","article-title":"Myocarditis, a rare but severe manifestation of Q fever: Report of 8 cases and review of the literature.","volume":"32","author":"Fournier","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3201\/eid1703.100882","article-title":"Q fever in France, 1985-2009.","volume":"17","author":"Frankel","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.3201\/eid1108.041354","article-title":"Coxiella burnetii genotyping.","volume":"11","author":"Glazunova","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-5833-8","article-title":"Extensive genome analysis of Coxiella burnetii reveals limited evolution within genomic groups.","volume":"20","author":"Hemsley","year":"2019","journal-title":"BMC Genom."},{"key":"B21","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1093\/ije\/22.5.945","article-title":"Q-fever is absent from New-Zealand.","volume":"22","author":"Hilbink","year":"1993","journal-title":"Int. J. Epidemiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2143-7","article-title":"Major differential gene regulation in Coxiella burnetii between in vivo and in vitro cultivation models.","volume":"16","author":"Kuley","year":"2015","journal-title":"BMC Genom."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01526","article-title":"Genome plasticity and polymorphisms in critical genes correlate with increased virulence of dutch outbreak-related Coxiella burnetii strains.","volume":"8","author":"Kuley","year":"2017","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-124","article-title":"Proteinortho : Detection of (Co-)orthologs in large-scale analysis.","volume":"12","author":"Lechner","year":"2011","journal-title":"BMC Bioinform."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1099\/ijsem.0.000760","article-title":"OrthoANI: An improved algorithm and software for calculating average nucleotide identity.","volume":"66","author":"Lee","year":"2016","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1023\/A:1007452503863","article-title":"An outbreak of sheep-associated Q fever in a rural community in Germany.","volume":"14","author":"Lyytik\u00e4inen","year":"1998","journal-title":"Eur. J. Epidemiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.3201\/eid1907.130044","article-title":"Unique clone of Coxiella burnetii causing severe Q fever, French Guiana.","volume":"19","author":"Mahamat","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/BF00145305","article-title":"Investigation of a Q-fever outbreak in northern Italy.","volume":"12","author":"Manfredi Selvaggi","year":"1996","journal-title":"Eur. J. Epidemiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/14787210.2020.1699055","article-title":"New insights in Coxiella burnetii infection: Diagnosis and therapeutic update.","volume":"18","author":"Melenotte","year":"2020","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1182\/blood-2015-04-639617","article-title":"B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.","volume":"127","author":"Melenotte","year":"2016","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"856","DOI":"10.3201\/eid2305.151159","article-title":"No such thing as chronic Q fever.","volume":"23","author":"Million","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.jvs.2006.09.016","article-title":"Coxiella burnetii infection of an aortic graft with multiple vertebral body erosion.","volume":"45","author":"O\u2019Donnell","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121619","article-title":"Characterization of Mate-type multidrug efflux pumps from Klebsiella pneumoniae MGH78578.","volume":"10","author":"Ogawa","year":"2015","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000056","article-title":"SNP-sites: Rapid efficient extraction of SNPs from multi-FASTA alignments.","volume":"2","author":"Page","year":"2016","journal-title":"Microb. Genom."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1093\/cid\/cix469","article-title":"Q Fever: Confusion between chronic infection and chronic fatigue.","volume":"65","author":"Raoult","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S1473-3099(05)70052-9","article-title":"Natural history and pathophysiology of Q fever.","volume":"5","author":"Raoult","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3201\/eid1704.101562","article-title":"Molecular epidemiology of Coxiella burnetii from ruminants in Q fever outbreak, the Netherlands.","volume":"17","author":"Roest","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1128\/iai.49.3.775-779.1985","article-title":"Correlation of plasmid type and disease caused by Coxiella burnetii.","volume":"49","author":"Samuel","year":"1985","journal-title":"Infect. Immun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation.","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"5455","DOI":"10.1073\/pnas.0931379100","article-title":"Complete genome sequence of the Q-fever pathogen Coxiella burnetii.","volume":"100","author":"Seshadri","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e00285","DOI":"10.1128\/genomeA.00285-14","article-title":"Draft genome sequences of six ruminant Coxiella burnetii isolates of European origin.","volume":"2","author":"Sidi-Boumedine","year":"2014","journal-title":"Genome Announc."},{"key":"B42","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/0954-6111(93)90006-L","article-title":"A large Q fever outbreak in the West Midlands: Clinical aspects.","volume":"87","author":"Smith","year":"1993","journal-title":"Respir. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1093\/jac\/49.2.379","article-title":"Mechanisms of resistance to fluoroquinolones in Coxiella burnetii.","volume":"49","author":"Spyridaki","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"B44","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.mib.2008.09.006","article-title":"Comparative genomics: The bacterial pan-genome.","volume":"11","author":"Tettelin","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1089\/mdr.2010.0015","article-title":"DNA gyrase and topoisomerase IV mutations in an in vitro fluoroquinolone-resistant Coxiella burnetii strain.","volume":"16","author":"Vranakis","year":"2010","journal-title":"Microb. Drug Resist."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1022356\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T18:42:29Z","timestamp":1669056149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1022356\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,21]]},"references-count":45,"alternative-id":["10.3389\/fmicb.2022.1022356"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.1022356","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,21]]},"article-number":"1022356"}}