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A novel echinocandin resistance mechanism involving an auxiliary copy of FKS1 in echinocandin\u2010producing fungus\n                    <jats:italic>Pezicula radicicola<\/jats:italic>\n                    NRRL 12192 was discovered. We sequenced the genome of NRRL 12192 and predicted two FKS1\u2010encoding genes (\n                    <jats:italic>prfks1n<\/jats:italic>\n                    and\n                    <jats:italic>prfks1a<\/jats:italic>\n                    ), rather than a single FKS1 gene typical of filamentous ascomycetes. The\n                    <jats:italic>prfks1a<\/jats:italic>\n                    gene sits immediately adjacent to an echinocandin (sporiofungin) gene cluster, which was confirmed by disruption of\n                    <jats:italic>prnrps4<\/jats:italic>\n                    and abolishment of sporiofungin production. Disruption of\n                    <jats:italic>prfks1a<\/jats:italic>\n                    dramatically increased the strain's sensitivity to exogenous echinocandins. In the absence of echinocandins, transcription levels of\n                    <jats:italic>prfks1a<\/jats:italic>\n                    relative to\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010tubulin in the wild type and in \u0394\n                    <jats:italic>prnrps4<\/jats:italic>\n                    stains were similar. Moreover,\n                    <jats:italic>prfks1a<\/jats:italic>\n                    is consistently transcribed at low levels and is upregulated in the presence of exogenous echinocandin, but not during growth conditions promoting endogenous production of sporiofungin. Therefore, we conclude that\n                    <jats:italic>prfks1a<\/jats:italic>\n                    is primarily responsible for protecting the fungus against extracellular echinocandin toxicity. The presence of unclustered auxiliary copies of FKS1 with high similarity to\n                    <jats:italic>prfks1a<\/jats:italic>\n                    in two other echinocandin\u2010producing strains suggests that this previously unrecognized resistance mechanism may be common in echinocandin\u2010producing fungi of the family Dermataceae of the class Leotiomycetes.\n                  <\/jats:p>","DOI":"10.1111\/1462-2920.14089","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T11:06:50Z","timestamp":1520852810000},"page":"3154-3167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genomics\u2010driven discovery of a novel self\u2010resistance mechanism in the echinocandin\u2010producing fungus\n                    <i>Pezicula radicicola<\/i>"],"prefix":"10.1111","volume":"20","author":[{"given":"Qun","family":"Yue","sequence":"first","affiliation":[{"name":"Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston Houston TX USA"},{"name":"Biotechnology Research Institute, Chinese Academy of Agricultural Sciences Beijing 100081 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston Houston TX USA"},{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences Beijing 100081 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology, Chinese Academy of Sciences Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology, Chinese Academy of Sciences Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"An","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-8417","authenticated-orcid":false,"given":"Gerald F","family":"Bills","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-002-0755-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx360"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/13693786.2012.675525"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00699-07"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2015.105"},{"key":"e_1_2_6_7_1","first-page":"133","article-title":"Measuring the distribution and diversity of antibiosis and secondary metabolites in the filamentous fungi","volume":"59","author":"Bills G.F.","year":"2009","journal-title":"Soc Indust Microbiol News"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja307220z"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a026334"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.funbio.2015.09.013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03256-14"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.6b00604"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-339"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf800595k"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12877"},{"key":"e_1_2_6_16_1","first-page":"22","article-title":"Neue Erkenntnisse aus einem pharmakologischen Pilz\u2010screening","volume":"39","author":"Dreyfuss M.M.","year":"1986","journal-title":"Sydowia"},{"key":"e_1_2_6_17_1","unstructured":"Dreyfuss M.M. andTscherter H.(1982) New metabolites processes for their production and their use. 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