{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:40:02Z","timestamp":1765485602475},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"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":["Infect Immun"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Coxiella burnetii<\/jats:named-content>is the bacterial agent of human Q fever, an acute, flu-like illness that can present as chronic endocarditis in immunocompromised individuals. Following aerosol-mediated transmission,<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>replicates in alveolar macrophages in a unique phagolysosome-like parasitophorous vacuole (PV) required for survival. The mechanisms of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>intracellular survival are poorly defined and a recent Q fever outbreak in the Netherlands emphasizes the need for better understanding this unique host-pathogen interaction. We recently demonstrated that inhibition of host cyclic AMP-dependent protein kinase (PKA) activity negatively impacts PV formation. In the current study, we confirmed PKA involvement in PV biogenesis and probed the role of PKA signaling during<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>infection of macrophages. Using PKA-specific inhibitors, we found the kinase was needed for biogenesis of prototypical PV and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>replication. PKA and downstream targets were differentially phosphorylated throughout infection, suggesting prolonged regulation of the pathway. Importantly, the pathogen actively triggered PKA activation, which was also required for PV formation by virulent<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>isolates during infection of primary human alveolar macrophages. A subset of PKA-specific substrates were differentially phosphorylated during<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>infection, suggesting the pathogen uses PKA signaling to control distinct host cell responses. Collectively, the current results suggest a versatile role for PKA in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. burnetii<\/jats:named-content>infection and indicate virulent organisms usurp host kinase cascades for efficient intracellular growth.<\/jats:p>","DOI":"10.1128\/iai.00101-12","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T04:59:56Z","timestamp":1333429196000},"page":"1980-1986","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Coxiella burnetii Alters Cyclic AMP-Dependent Protein Kinase Signaling during Growth in Macrophages"],"prefix":"10.1128","volume":"80","author":[{"given":"Laura J.","family":"MacDonald","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Kurten","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"},{"name":"Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Voth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00301-09"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.40.3.1155-1162.1983"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.595"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00175-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040544"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1163"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5816-5821.2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204652200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00688-10"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002056"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201002108"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1016-8478(23)07332-6","article-title":"Regulation of BAD protein by PKA, PKC\u03b4, and phosphatases in adult rat cardiac myocytes subjected to oxidative stress","volume":"24","author":"Cieslak D","year":"2007","unstructured":"CieslakDLazouA. 2007. 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