{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:06:09Z","timestamp":1753877169682,"version":"3.41.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"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 Natural Science Fund Youth Project","award":["81700007"],"award-info":[{"award-number":["81700007"]}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["2019A10"],"award-info":[{"award-number":["2019A10"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:label\/>\n                  <jats:p>Azoles were used as the primary antifungal agents to treat the Cryptococcus gattii infection. Evidence showed that subtypes of C. gattii respond differently to azoles, but the mechanism is largely elusive. In this study, we aimed to find the mechanisms of differences in azole drug susceptibility in different subtypes of C. gattii. Eight clinical strains of C. gattii were collected for molecular typing, multilocus sequence typing (MLST) analysis, and antifungal susceptibility testing. Based on drug susceptibility differences, the RNA sequencing data were analyzed to find candidate azole drug susceptibility genes, and qPCR validation was performed. Five VGI subtypes and three VGII subtypes were identified among the eight strains of C. gattii. The clinical isolates showed high genetic diversity, and seven sequence types (STs) were identified. The geometric mean (GM) of minimum inhibitory concentration (MIC) for fluconazole, voriconazole, and itraconazole of VGI subtype was significantly lower than that of VGII subtype, and genes related to transporter activities were differentially expressed between VGI and VGII strains. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs (differential expressed genes) were found to be enriched in multiple ABC transporters. We further performed qPCR to quantify the expression level of seven ABC transporters. We found that ABC transporters ATM1, MDR1, PDR5, PDR5-3, and PXA2 were expressed significantly higher in VGII strains than in VGI strains. Our work revealed four novel ABC transporters, ATM1, PDR5, PDR5-3, and PXA2, promising candidate targets regulating azole susceptibility in C. gattii strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Azoles were used as the primary antifungal agents for treating Cryptococuss gattii infection. Since subtypes of C. gattii respond differently to azoles. We analyzed mRNA expression profiles of different subtypes and identified four ABC transporters that could be potential genes regulating azole sensitivity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mmy\/myac035","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T01:16:40Z","timestamp":1654046200000},"source":"Crossref","is-referenced-by-count":3,"title":["Significance of differential expression profiles of ABC transporters in azole susceptibility between <i>Cryptococcus gattii<\/i> VGI and VGII strains"],"prefix":"10.1093","volume":"60","author":[{"given":"Xinying","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University; Peking University Ninth School of Clinical Medicine , Haidian District, Beijing 100871, China"},{"name":"Department of Respiratory and Critical Care, Chinese PLA General Hospital , 28 Fuxing Road, Beijing 100853, China"},{"name":"Affiliated Hospital of Weifang Medical University , Weifang, Shandong 261032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelei","family":"Zang","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA , 28 Fuxing Road, Beijing 100853, China"},{"name":"Medical laboratory center, the First Medical Centre, Chinese PLA General Hospital , 28 Fuxing Road, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital , Dongcheng District, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical laboratory center, the First Medical Centre, Chinese PLA General Hospital , 28 Fuxing Road, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of clinical laboratory, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College , Haikou, Hanon 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xidong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care, Chinese PLA General Hospital , 28 Fuxing Road, Beijing 100853, China"},{"name":"Medical School of Chinese PLA , 28 Fuxing Road, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cadres, 971 Hospital of the Chinese People's Liberation Army Navy , No.\u00a022 Minjiang Road, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hengyu","family":"Deng","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Weifang Medical University , Weifang, Shandong 261032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medical Imaging, Binzhou Medical University , Laishan District, Yantai 256603, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University; Peking University Ninth School of Clinical Medicine , Haidian District, Beijing 100871, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingxia","family":"Shen","sequence":"additional","affiliation":[{"name":"Medical laboratory center, the First Medical Centre, Chinese PLA General 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