{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:00:20Z","timestamp":1776132020252,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>\n<jats:italic>Candida albicans<\/jats:italic>, the main human fungal pathogen, can cause fungal infection and seriously affect people's health and life. This study aimed to investigate the effects of ritonavir (RIT) on <jats:italic>C. albicans<\/jats:italic> and the correlation between <jats:italic>SAP2<\/jats:italic> as well as <jats:italic>ERG11<\/jats:italic> and drug resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Secreted aspartyl proteinases (Saps) activities and pathogenicity of <jats:italic>C. albicans<\/jats:italic> with different drug resistance were measured. M27\u2010A4 broth microdilution method was used to analyze the drug sensitivity of RIT combined with fluconazole (FCA) on <jats:italic>C. albicans<\/jats:italic>. After that, <jats:italic>SAP2<\/jats:italic> and <jats:italic>ERG11<\/jats:italic> mutations were examined by polymerase chain reaction (PCR) and sequencing, and quantitative real\u2010time PCR was utilized to determine the expression of the two genes. By analyzing <jats:italic>p<\/jats:italic>z values, the Saps activity of cross\u2010resistant strains was the highest, followed by voriconazole (VRC)\u2010resistant strains, FCA\u2010resistant strains, itraconazole (ITR)\u2010resistant strains, and sensitive strains. The pathogenicity of <jats:italic>C. albicans<\/jats:italic> in descending order was as follows: cross\u2010resistant strains, VRC\u2010resistant strains, ITR\u2010resistant strains, FCA\u2010resistant strains, and sensitive strains. With the increase of RIT concentrations, the Saps activity was gradually inhibited. Drug sensitivity results showed that there was no synergistic effect between RIT and FCA. Additionally, no gene mutation sites were found in <jats:italic>SAP2<\/jats:italic> sequencing, and 17 synonymous mutations and 6 missense mutations occurred in <jats:italic>ERG11<\/jats:italic> sequencing. Finally, the expression of <jats:italic>SAP2<\/jats:italic> and <jats:italic>ERG11<\/jats:italic> was significantly higher in the resistant strains compared with the sensitive strains, and there was a positive liner correlation between <jats:italic>SAP2<\/jats:italic> and <jats:italic>ERG11<\/jats:italic> messenger RNA expression (<jats:italic>r<\/jats:italic>\u2009=\u2009.6655, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings may help to improve our understanding of azole\u2010resistant mechanisms of <jats:italic>C. albicans<\/jats:italic> and provide a novel direction for clinical therapeutics of <jats:italic>C. albicans<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.415","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T09:05:34Z","timestamp":1620291934000},"page":"667-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles\u2010resistant strains of <i>Candida albicans<\/i> as well as regulatory role of <i>SAP2<\/i> and <i>ERG11<\/i>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-7401","authenticated-orcid":false,"given":"Wenli","family":"Feng","sequence":"first","affiliation":[{"name":"The Department of Dermatovenereology The Second Hospital of Shanxi Medical University  Taiyuan Shanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"The Department of Dermatovenereology The Second 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