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RTA-like proteins, a distinctive class of transmembrane fungal proteins, are involved in several stress responses. Nonetheless, their role in fungal azole resistance is yet to be determined. Transcriptomic studies performed in this investigation revealed that azole stimulation significantly upregulates the expression of RTA-like proteins in\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    . Phenotypic analyses indicated that relative to the wild-type strain, the\n                    <jats:italic>\u0394rta1<\/jats:italic>\n                    ,\n                    <jats:italic>\u0394rta5<\/jats:italic>\n                    and\n                    <jats:italic>\u0394rta7<\/jats:italic>\n                    mutants exhibited increased sensitivity to antifungal agents, including azoles and amphotericin B (AmB). RNA sequencing and real-time quantitative polymerase chain reaction indicated a significant upregulation of the oxidoreductase gene\n                    <jats:italic>oxrA<\/jats:italic>\n                    , which is integral to the oxidative stress response, in the\n                    <jats:italic>\u0394rta1<\/jats:italic>\n                    ,\n                    <jats:italic>\u0394rta5<\/jats:italic>\n                    and\n                    <jats:italic>\u0394rta7<\/jats:italic>\n                    mutants. Furthermore, the\n                    <jats:italic>oxrA<\/jats:italic>\n                    overexpression strain (OE::\n                    <jats:italic>oxrA<\/jats:italic>\n                    ) displayed increased tolerance to oxidative stress, yet paradoxically, it also showed a considerable hike in sensitivity to azole and AmB. This heightened drug sensitivity was correlated with the downregulation of most drug efflux pump genes. In conclusion, the RTA-like proteins Rta1, Rta5 and Rta7 possibly modulate azole susceptibility in\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    by regulating\n                    <jats:italic>oxrA<\/jats:italic>\n                    expression, subsequently affecting the transcription of drug efflux pump genes. As proteins specific to fungi, members of the RTA family are promising targets for the development of novel antifungal therapeutics.\n                  <\/jats:p>","DOI":"10.1186\/s12866-026-04985-x","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T02:56:15Z","timestamp":1776048975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RTA-like proteins regulate azole susceptibility by affecting the expression of the oxidoreductase gene oxrA in Aspergillus fumigatus"],"prefix":"10.1186","volume":"26","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-652X","authenticated-orcid":false,"given":"Xiaogang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"issue":"1","key":"4985_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1055\/s-0043-1777769","volume":"45","author":"J Heylen","year":"2024","unstructured":"Heylen J, Vanbiervliet Y, Maertens J, Rijnders B, Wauters J. 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