{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:36:27Z","timestamp":1781105787936,"version":"3.54.1"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,6,12]]},"abstract":"<jats:p>\n                    Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis.\n                    <jats:italic>Bartonella<\/jats:italic>\n                    effector protein A (BepA) of vasculotumorigenic\n                    <jats:italic>Bartonella henselae<\/jats:italic>\n                    protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the \u03b1-subunit of the AC-stimulating G protein (G\u03b1s) were identified as potential cellular target proteins for BepA by gel-free proteomics. Results of the proteomics screen were evaluated for physical and functional interaction by: (\n                    <jats:italic>i<\/jats:italic>\n                    ) a heterologous in vivo coexpression system, where human AC activity was reconstituted under the regulation of G\u03b1s and BepA in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ; (\n                    <jats:italic>ii<\/jats:italic>\n                    ) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and G\u03b1s; (\n                    <jats:italic>iii<\/jats:italic>\n                    ) surface plasmon resonance experiments; and (\n                    <jats:italic>iv<\/jats:italic>\n                    ) an in vivo fluorescence bimolecular complementation-analysis. The data demonstrate that BepA directly binds host cell AC to potentiate the G\u03b1s-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein \u03b1-subunits by cholera and pertussis toxins, the fundamentally different BepA-mediated elevation of host cell cAMP concentration appears subtle and is dependent on the stimulus of a G protein-coupled receptor-released G\u03b1s. We propose that this mechanism contributes to the persistence of\n                    <jats:italic>Bartonella henselae<\/jats:italic>\n                    in the chronically infected vascular endothelium.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1117651109","type":"journal-article","created":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T23:18:12Z","timestamp":1337987892000},"page":"9581-9586","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Bacterial effector binds host cell adenylyl cyclase to potentiate G\u03b1s-dependent cAMP production"],"prefix":"10.1073","volume":"109","author":[{"given":"Arto T.","family":"Pulliainen","sequence":"first","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Pieles","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron S.","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hauert","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Quebatte","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wepf","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule, CH-8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gstaiger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule, CH-8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruedi","family":"Aebersold","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule, CH-8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen W.","family":"Dessauer","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Dehio","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,5,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.019"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900160106"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408410490468795"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.6.2669"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.10.3129"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)39173-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08123"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604017103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00324.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072292699"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2003.03964.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020115"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406796102"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7792604"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(74)90222-X"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203962200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000166277"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.35.22265"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5345.1907"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1929"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1877-1173(10)91004-1"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-17969-3_2"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)45019-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1117651109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:30:13Z","timestamp":1649799013000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1117651109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,25]]},"references-count":23,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2012,6,12]]}},"alternative-id":["10.1073\/pnas.1117651109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1117651109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,25]]},"assertion":[{"value":"2012-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}