The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11
Abstract Background Candida albicans, 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 C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance. Re...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.415 |
| _version_ | 1819128766885003264 |
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| author | Wenli Feng Jing Yang Yan Ma Zhiqin Xi Xiaoqin Zhao Xiaoxia Zhao Min Zhao |
| author_facet | Wenli Feng Jing Yang Yan Ma Zhiqin Xi Xiaoqin Zhao Xiaoxia Zhao Min Zhao |
| author_sort | Wenli Feng |
| collection | DOAJ |
| description | Abstract Background Candida albicans, 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 C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance. Results Secreted aspartyl proteinases (Saps) activities and pathogenicity of C. albicans with different drug resistance were measured. M27‐A4 broth microdilution method was used to analyze the drug sensitivity of RIT combined with fluconazole (FCA) on C. albicans. After that, SAP2 and ERG11 mutations were examined by polymerase chain reaction (PCR) and sequencing, and quantitative real‐time PCR was utilized to determine the expression of the two genes. By analyzing pz values, the Saps activity of cross‐resistant strains was the highest, followed by voriconazole (VRC)‐resistant strains, FCA‐resistant strains, itraconazole (ITR)‐resistant strains, and sensitive strains. The pathogenicity of C. albicans in descending order was as follows: cross‐resistant strains, VRC‐resistant strains, ITR‐resistant strains, FCA‐resistant 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 SAP2 sequencing, and 17 synonymous mutations and 6 missense mutations occurred in ERG11 sequencing. Finally, the expression of SAP2 and ERG11 was significantly higher in the resistant strains compared with the sensitive strains, and there was a positive liner correlation between SAP2 and ERG11 messenger RNA expression (r = .6655, p < .001). Conclusion These findings may help to improve our understanding of azole‐resistant mechanisms of C. albicans and provide a novel direction for clinical therapeutics of C. albicans infection. |
| first_indexed | 2024-12-22T08:33:03Z |
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| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-12-22T08:33:03Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
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| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-66a941da1a9345ab928d84f6faeeabc42022-12-21T18:32:26ZengWileyImmunity, Inflammation and Disease2050-45272021-09-019366768010.1002/iid3.415The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11Wenli Feng0Jing Yang1Yan Ma2Zhiqin Xi3Xiaoqin Zhao4Xiaoxia Zhao5Min Zhao6The Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaThe Department of Dermatovenereology The Second Hospital of Shanxi Medical University Taiyuan Shanxi ChinaAbstract Background Candida albicans, 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 C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance. Results Secreted aspartyl proteinases (Saps) activities and pathogenicity of C. albicans with different drug resistance were measured. M27‐A4 broth microdilution method was used to analyze the drug sensitivity of RIT combined with fluconazole (FCA) on C. albicans. After that, SAP2 and ERG11 mutations were examined by polymerase chain reaction (PCR) and sequencing, and quantitative real‐time PCR was utilized to determine the expression of the two genes. By analyzing pz values, the Saps activity of cross‐resistant strains was the highest, followed by voriconazole (VRC)‐resistant strains, FCA‐resistant strains, itraconazole (ITR)‐resistant strains, and sensitive strains. The pathogenicity of C. albicans in descending order was as follows: cross‐resistant strains, VRC‐resistant strains, ITR‐resistant strains, FCA‐resistant 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 SAP2 sequencing, and 17 synonymous mutations and 6 missense mutations occurred in ERG11 sequencing. Finally, the expression of SAP2 and ERG11 was significantly higher in the resistant strains compared with the sensitive strains, and there was a positive liner correlation between SAP2 and ERG11 messenger RNA expression (r = .6655, p < .001). Conclusion These findings may help to improve our understanding of azole‐resistant mechanisms of C. albicans and provide a novel direction for clinical therapeutics of C. albicans infection.https://doi.org/10.1002/iid3.415Candida albicansERG11SAP2secreted aspartyl proteinases |
| spellingShingle | Wenli Feng Jing Yang Yan Ma Zhiqin Xi Xiaoqin Zhao Xiaoxia Zhao Min Zhao The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 Immunity, Inflammation and Disease Candida albicans ERG11 SAP2 secreted aspartyl proteinases |
| title | The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 |
| title_full | The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 |
| title_fullStr | The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 |
| title_full_unstemmed | The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 |
| title_short | The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11 |
| title_sort | effects of secreted aspartyl proteinase inhibitor ritonavir on azoles resistant strains of candida albicans as well as regulatory role of sap2 and erg11 |
| topic | Candida albicans ERG11 SAP2 secreted aspartyl proteinases |
| url | https://doi.org/10.1002/iid3.415 |
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