Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance
<i>Trichosporon asahii</i> is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underly...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/2076-2607/11/11/2798 |
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| author | Xiaoping Ma Wanling Yang Aining Yang Dong Chen Chengdong Wang Shanshan Ling Sanjie Cao Zhicai Zuo Ya Wang Zhijun Zhong Guangneng Peng Ming He Yu Gu |
| author_facet | Xiaoping Ma Wanling Yang Aining Yang Dong Chen Chengdong Wang Shanshan Ling Sanjie Cao Zhicai Zuo Ya Wang Zhijun Zhong Guangneng Peng Ming He Yu Gu |
| author_sort | Xiaoping Ma |
| collection | DOAJ |
| description | <i>Trichosporon asahii</i> is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of <i>T. asahii</i> and explore farnesol’s effects on these processes. A comparative metabolome–transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) <i>T. asahii</i> strains, and 25 μM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs. YAN and PB-25 vs. PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in <i>T. asahii</i> was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use. |
| first_indexed | 2024-03-09T16:35:33Z |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T16:35:33Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-bbef36b1c1e44633aaeea5b307bda7f22023-11-24T14:57:18ZengMDPI AGMicroorganisms2076-26072023-11-011111279810.3390/microorganisms11112798Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole ToleranceXiaoping Ma0Wanling Yang1Aining Yang2Dong Chen3Chengdong Wang4Shanshan Ling5Sanjie Cao6Zhicai Zuo7Ya Wang8Zhijun Zhong9Guangneng Peng10Ming He11Yu Gu12Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaSichuan Provincial Center for Animal Disease Prevention and Control, Chengdu 610041, ChinaChina Conservation and Research Center for the Giant Panda, Chengdu 611800, ChinaChina Conservation and Research Center for the Giant Panda, Chengdu 611800, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaCollege of Life Sciences, Sichuan Agricultural University, Chengdu 611130, China<i>Trichosporon asahii</i> is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of <i>T. asahii</i> and explore farnesol’s effects on these processes. A comparative metabolome–transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) <i>T. asahii</i> strains, and 25 μM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs. YAN and PB-25 vs. PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in <i>T. asahii</i> was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use.https://www.mdpi.com/2076-2607/11/11/2798fluconazole resistance<i>Trichosporon asahii</i>farnesolmetabolometranscriptome |
| spellingShingle | Xiaoping Ma Wanling Yang Aining Yang Dong Chen Chengdong Wang Shanshan Ling Sanjie Cao Zhicai Zuo Ya Wang Zhijun Zhong Guangneng Peng Ming He Yu Gu Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance Microorganisms fluconazole resistance <i>Trichosporon asahii</i> farnesol metabolome transcriptome |
| title | Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance |
| title_full | Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance |
| title_fullStr | Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance |
| title_full_unstemmed | Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance |
| title_short | Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of <i>Trichosporon asahii</i> and the Role of Farnesol in Fluconazole Tolerance |
| title_sort | metabolome and transcriptome combinatory profiling reveals fluconazole resistance mechanisms of i trichosporon asahii i and the role of farnesol in fluconazole tolerance |
| topic | fluconazole resistance <i>Trichosporon asahii</i> farnesol metabolome transcriptome |
| url | https://www.mdpi.com/2076-2607/11/11/2798 |
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