{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T10:28:12Z","timestamp":1664447292060},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Science and Technology Major Project of China","award":["2017ZX09101003-001-017"],"award-info":[{"award-number":["2017ZX09101003-001-017"]}]},{"name":"Key Research and Development Plan","award":["201703D111033"],"award-info":[{"award-number":["201703D111033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multi-alterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemo-sensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23\u201340.00\u00a0\u03bcg\/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10\u00a0mg\/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08\u20132.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52\u201355.33% decrease of cytochrome P450 lanosterol 14\u03b1-demethylase, glucan 1, 3-\u03b2 glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency.<\/jats:p>","DOI":"10.1093\/mmy\/myaa070","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T11:10:20Z","timestamp":1598440220000},"page":"515-527","source":"Crossref","is-referenced-by-count":1,"title":["Antifungal resistance-modifying multiplexing action of <i>Momordica charantia<\/i> protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in <i>Candida albicans<\/i>"],"prefix":"10.1093","volume":"59","author":[{"given":"Qiao","family":"Yuan-Biao","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory of Innovative Drugs for the Treatment of Serious Diseases Basing on Chronic Inflammation, College of Traditional Chinese Medicines, Shanxi University of Chinese Medicine, Taiyuan, Shanxi 030619, P. R. China"},{"name":"Graduate Institute of Pharmaceutical Chemistry, Luliang University, Luliang, Shanxi 033001, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Lan-Fang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Innovative Drugs for the Treatment of Serious Diseases Basing on Chronic Inflammation, College of Traditional Chinese Medicines, Shanxi University of Chinese Medicine, Taiyuan, Shanxi 030619, P. R. 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