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These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    genome. We found that invasive growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This\n                    <jats:italic>in vivo<\/jats:italic>\n                    transcriptional response is largely mimicked by\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth in\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    minimal medium that is deficient in nitrogen, iron, and\/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during\n                    <jats:italic>in vivo<\/jats:italic>\n                    growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was\n                    <jats:italic>rlmA<\/jats:italic>\n                    , which is required for the organism to achieve maximal fungal burden in the lung. The other was\n                    <jats:italic>sltA<\/jats:italic>\n                    , which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of\n                    <jats:italic>laeA<\/jats:italic>\n                    . Using deletion and overexpression mutants, we determined that the attenuated virulence of the \u0394\n                    <jats:italic>sltA<\/jats:italic>\n                    mutant is due in part to decreased expression\n                    <jats:italic>aspf1<\/jats:italic>\n                    , which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus,\n                    <jats:italic>in vivo<\/jats:italic>\n                    transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009235","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T13:39:16Z","timestamp":1617025156000},"page":"e1009235","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung"],"prefix":"10.1371","volume":"17","author":[{"given":"Hong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6978-9087","authenticated-orcid":true,"given":"Wenjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh T.","family":"Phan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma V.","family":"Solis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-3468","authenticated-orcid":true,"given":"Carol A.","family":"Woolford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-7649","authenticated-orcid":true,"given":"Amol C.","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-9727","authenticated-orcid":true,"given":"Carrie","family":"McCraken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-6304","authenticated-orcid":true,"given":"Jianfeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-0201","authenticated-orcid":true,"given":"Michael 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