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Diseases","award":["R01AI153356"],"award-info":[{"award-number":["R01AI153356"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["2021\/04977-5 (GHG)"],"award-info":[{"award-number":["2021\/04977-5 (GHG)"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["2023\/00206-0 (ED)"],"award-info":[{"award-number":["2023\/00206-0 (ED)"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["2022\/02992-0 (TF)"],"award-info":[{"award-number":["2022\/02992-0 (TF)"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["301058\/2019-9"],"award-info":[{"award-number":["301058\/2019-9"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["404735\/2018-5"],"award-info":[{"award-number":["404735\/2018-5"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["405934\/2022-0"],"award-info":[{"award-number":["405934\/2022-0"]}]},{"name":"Joint Canada-Israel Health Research Program","award":["R01AI153356"],"award-info":[{"award-number":["R01AI153356"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aspergillus fumigatus can cause invasive pulmonary aspergillosis (IPA). Fungicidal azoles and fungistatic caspofungin (CAS) are the first- and second-line therapies, respectively, used to treat IPA. Treatment of A. fumigatus with CAS or micafungin induces the production of the oxylipin 5,8-diHODE by the fungal oxygenase PpoA. For this article, we investigated the influence of ppo genes, which encode the fatty acid oxygenases responsible for oxylipin biosynthesis, on CAS tolerance. The influence of PpoA and PpoC on CAS tolerance is mediated by MpkA phosphorylation and protein kinase A (PKA) activity. RNAseq transcriptional profiling and the label-free quantitative proteomics of the ppoA and ppoC mutants showed that differentially expressed genes and proteins are related to secondary metabolites and carbohydrate metabolism. We also characterized two clinical isolates, CM7555 and IFM61407, which decrease and increase susceptibility to CAS, respectively. CM7555 does not exhibit increased oxylipin production in the presence of CAS but oxylipin induction upon CAS exposure is increased in IFM61407, suggesting that oxylipins are not the only mechanism involved in CAS tolerance in these isolates. Upon CAS exposure, CM7555 has higher MpkA phosphorylation and PKA activity than IFM61407. Our results reveal the different aspects and genetic determinants involved in A. fumigatus CAS tolerance.<\/jats:p>","DOI":"10.3390\/jof10110749","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:11:24Z","timestamp":1730279484000},"page":"749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Influence of Aspergillus fumigatus Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-9046","authenticated-orcid":false,"given":"Endrews","family":"Delbaje","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Alves","family":"de Castro","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante G.","family":"Calise","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1647-5003","authenticated-orcid":false,"given":"Niu","family":"Mengyao","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Augusta Crivelente","family":"Horta","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2859-1992","authenticated-orcid":false,"given":"Daniel Yuri","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, State University of Campinas (Unicamp), Campinas 13083-862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-7809","authenticated-orcid":false,"given":"Jo\u00e3o Guilherme","family":"Pontes","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, State University of Campinas (Unicamp), Campinas 13083-862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta\u00edcia","family":"Fill","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, State University of Campinas (Unicamp), Campinas 13083-862, Brazil"},{"name":"National Institutes of Science and Technology in Human Pathogenic Fungi, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-6402","authenticated-orcid":false,"given":"Olaf","family":"Kniemeyer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-3853","authenticated-orcid":false,"given":"Thomas","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel A.","family":"Brakhage","sequence":"additional","affiliation":[{"name":"Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany"},{"name":"Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9264-5118","authenticated-orcid":false,"given":"Koon Ho","family":"Wong","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"},{"name":"Institute of Translational Medicine, Faculty of Health Sciences, University of Macaugrid, Avenida da Universidade, Taipa, Macau SAR 999078, China"},{"name":"MoE Frontiers Science Center for Precision Oncology, University of Macaugrid, Taipa, Macau SAR 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-9473","authenticated-orcid":false,"given":"Nancy 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13054-014-0722-7","article-title":"Epidemiology of invasive aspergillosis in critically ill patients: Clinical presentation, underlying conditions, and outcomes","volume":"19","author":"Taccone","year":"2015","journal-title":"Crit. 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