{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T23:16:58Z","timestamp":1773443818110,"version":"3.50.1"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Israel-Italy cooperation Grant"},{"name":"ERA0Net Pathogenomics Oxystress","award":["0315902B"],"award-info":[{"award-number":["0315902B"]}]},{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["996-47.12\/2008"],"award-info":[{"award-number":["996-47.12\/2008"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            is the most common pathogenic mold infecting humans and a significant cause of morbidity and mortality in immunocompromised patients. In invasive pulmonary aspergillosis,\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            spores are inhaled into the lungs, undergoing germination and invasive hyphal growth. The fungus occludes and disrupts the blood vessels, leading to hypoxia and eventual tissue necrosis. The ability of this mold to adapt to hypoxia is regulated in part by the sterol regulatory element binding protein (SREBP) SrbA and the DscA to DscD Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage. Loss of the genes encoding these proteins results in avirulence. To identify novel regulators of hypoxia sensing, we screened the\n            <jats:named-content content-type=\"genus-species\">Neurospora crassa<\/jats:named-content>\n            gene deletion library under hypoxia and identified a novel rhomboid family protease essential for hypoxic growth. Deletion of the\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            rhomboid homolog\n            <jats:italic>rbdA<\/jats:italic>\n            resulted in an inability to grow under hypoxia, hypersensitivity to CoCl\n            <jats:sub>2<\/jats:sub>\n            , nikkomycin Z, fluconazole, and ferrozine, abnormal swollen tip morphology, and transcriptional dysregulation\u2014accurately phenocopying deletion of\n            <jats:italic>srbA. In vivo<\/jats:italic>\n            ,\n            <jats:italic>rbdA<\/jats:italic>\n            deletion resulted in increased sensitivity to phagocytic killing, a reduced inflammatory Th1 and Th17 response, and strongly attenuated virulence. Phenotypic rescue of the \u0394\n            <jats:italic>rbdA<\/jats:italic>\n            mutant was achieved by expression and nuclear localization of the N terminus of SrbA, including its HLH domain, further indicating that RbdA and SrbA act in the same signaling pathway. In summary, we have identified RbdA, a novel putative rhomboid family protease in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            that mediates hypoxia adaptation and fungal virulence and that is likely linked to SrbA cleavage and activation.\n          <\/jats:p>","DOI":"10.1128\/iai.00011-16","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T03:23:49Z","timestamp":1460431429000},"page":"1866-1878","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence"],"prefix":"10.1128","volume":"84","author":[{"given":"Yakir","family":"Vaknin","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falk","family":"Hillmann","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute (HKI), Jena, Germany"},{"name":"Friedrich Schiller University, Institute of Microbiology, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Iannitti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi di Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Netali","family":"Ben Baruch","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Sandovsky-Losica","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yona","family":"Shadkchan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigina","family":"Romani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi di Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Brakhage","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute (HKI), Jena, Germany"},{"name":"Friedrich Schiller University, Institute of Microbiology, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-6402","authenticated-orcid":false,"given":"Olaf","family":"Kniemeyer","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute (HKI), Jena, Germany"},{"name":"Friedrich Schiller University, Institute of Microbiology, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Osherov","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2008.05.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019737"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02104-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945005774912717"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.6.889"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08034.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00084-14"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12679"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-015-0487-9"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004487"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05027-11"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.080440-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.01.012"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030022"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.317370"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.02.035"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00252-12"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-611-5_3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00126-10"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01408.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-539-8_33"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201305-0986OC"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-001-0589-6"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2130"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01633"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.10.165"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003575"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00469"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.66.11.4810-4816.2000"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002145"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002374"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00358-09"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06895.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800039200"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-012944"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-11-1540"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072307"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00011-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00011-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:17:10Z","timestamp":1646475430000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00011-16"}},"subtitle":[],"editor":[{"suffix":"Jr.","given":"G. S.","family":"Deepe","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1128\/IAI.00011-16"],"URL":"https:\/\/doi.org\/10.1128\/iai.00011-16","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"2016-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}