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Genet"],"abstract":"<jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    causes a range of human and animal diseases collectively known as aspergillosis.\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    mycotoxin with a wide range of known toxic effects that impair human immune cell function. GT is also highly toxic to\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    and this fungus has evolved self-protection mechanisms that include (i) the GT efflux pump GliA, (ii) the GT neutralising enzyme GliT, and (iii) the negative regulation of GT biosynthesis by the\n                    <jats:italic>bis<\/jats:italic>\n                    -thiomethyltransferase GtmA. The transcription factor (TF) RglT is the main regulator of GliT and this GT protection mechanism also occurs in the non-GT producing fungus\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>nidulans<\/jats:italic>\n                    . However, the\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>nidulans<\/jats:italic>\n                    genome does not encode GtmA and GliA. This work aimed at analysing the transcriptional response to exogenous GT in\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    and\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>nidulans<\/jats:italic>\n                    , two distantly related\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    species, and to identify additional components required for GT protection. RNA-sequencing shows a highly different transcriptional response to exogenous GT with the RglT-dependent regulon also significantly differing between\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    and\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>nidulans<\/jats:italic>\n                    . However, we were able to observe homologs whose expression pattern was similar in both species (43 RglT-independent and 11 RglT-dependent). Based on this approach, we identified a novel RglT-dependent methyltranferase, MtrA, involved in GT protection. Taking into consideration the occurrence of RglT-independent modulated genes, we screened an\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    deletion library of 484 transcription factors (TFs) for sensitivity to GT and identified 15 TFs important for GT self-protection. Of these, the TF KojR, which is essential for kojic acid biosynthesis in\n                    <jats:italic>Aspergillus oryzae<\/jats:italic>\n                    , was also essential for virulence and GT biosynthesis in\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    , and for GT protection in\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    ,\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>nidulans<\/jats:italic>\n                    , and\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>oryzae<\/jats:italic>\n                    . KojR regulates\n                    <jats:italic>rglT<\/jats:italic>\n                    ,\n                    <jats:italic>gliT<\/jats:italic>\n                    ,\n                    <jats:italic>gliJ<\/jats:italic>\n                    expression and sulfur metabolism in\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    species. Together, this study identified conserved components required for GT protection in\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    species.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009965","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T15:20:51Z","timestamp":1642519251000},"page":"e1009965","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Regulation of gliotoxin biosynthesis and protection in Aspergillus species"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3045-6511","authenticated-orcid":true,"given":"Patr\u00edcia Alves","family":"de Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina","family":"Colabardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-9329","authenticated-orcid":true,"given":"Ma\u00edsa","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2159-5296","authenticated-orcid":true,"given":"Maria Augusta Crivelente","family":"Horta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6295-231X","authenticated-orcid":true,"given":"Sonja L.","family":"Knowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-9463","authenticated-orcid":true,"given":"Huzefa A.","family":"Raja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-8464","authenticated-orcid":true,"given":"Nicholas H.","family":"Oberlies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-3307","authenticated-orcid":true,"given":"Yasuji","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-8072","authenticated-orcid":true,"given":"Katsuya","family":"Gomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8436-595X","authenticated-orcid":true,"given":"Jacob L.","family":"Steenwyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Rokas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-3663","authenticated-orcid":true,"given":"Relber A.","family":"Gon\u00e7ales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-0753","authenticated-orcid":true,"given":"Cl\u00e1udio","family":"Duarte-Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-8030","authenticated-orcid":true,"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-3159","authenticated-orcid":true,"given":"Laure N. 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