Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans

Candida albicans is a common fungal pathogen that can cause life-threatening infections. MIR1 is considered to be a mitochondrial phosphate carrier of C. albicans, while its role in virulence has not been fully elucidated. In this study, we found that mir1Δ/Δ mutant exhibited severe virulence defect...

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Main Authors: Qiao-Ling Hu, Hua Zhong, Xin-Rong Wang, Lei Han, Shan-Shan Ma, Ling Li, Yan Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-01-01
Series:Mycology
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Online Access:https://www.tandfonline.com/doi/10.1080/21501203.2024.2354876
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author Qiao-Ling Hu
Hua Zhong
Xin-Rong Wang
Lei Han
Shan-Shan Ma
Ling Li
Yan Wang
author_facet Qiao-Ling Hu
Hua Zhong
Xin-Rong Wang
Lei Han
Shan-Shan Ma
Ling Li
Yan Wang
author_sort Qiao-Ling Hu
collection DOAJ
description Candida albicans is a common fungal pathogen that can cause life-threatening infections. MIR1 is considered to be a mitochondrial phosphate carrier of C. albicans, while its role in virulence has not been fully elucidated. In this study, we found that mir1Δ/Δ mutant exhibited severe virulence defect in both nematode and murine models. Further mechanism studies revealed that the mir1Δ/Δ mutant grew more slowly than the wild-type strain and showed severe filamentation defects on the hypha-inducing agar media, including YPD + serum, Lee, Spider + glucose, SLAD, SLD, and YPS. Furthermore, the loss of MIR1 resulted in unfermentable carbon utilisation defect, ATP decrease, and reactive oxygen species (ROS) accumulation in C. albicans. Antioxidant proanthocyanidins, vitamin E, and N-acetyl cysteine (NAC) could reduce intracellular ROS levels and partially rescue the filamentation defects of the mir1Δ/Δ mutant. Accordingly, hypha-specific genes, as well as CEK1 and RIM101 were down-regulated in the mir1Δ/Δ mutant, and this down-regulation could be partially rescued by the addition of the antioxidant NAC. Collectively, MIR1 plays an important role in C. albicans mitochondrial function, filamentation and virulence, and would be a promising antifungal target.
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spelling doaj-art-3a935ca75bc7445681d2602b90359fd62025-08-20T02:29:55ZengTaylor & Francis GroupMycology2150-12032150-12112025-01-0116136938110.1080/21501203.2024.2354876Mitochondrial phosphate carrier plays an important role in virulence of Candida albicansQiao-Ling Hu0Hua Zhong1Xin-Rong Wang2Lei Han3Shan-Shan Ma4Ling Li5Yan Wang6School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaSchool of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai, ChinaSchool of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai, ChinaSchool of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaSchool of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai, ChinaSchool of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai, ChinaSchool of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCandida albicans is a common fungal pathogen that can cause life-threatening infections. MIR1 is considered to be a mitochondrial phosphate carrier of C. albicans, while its role in virulence has not been fully elucidated. In this study, we found that mir1Δ/Δ mutant exhibited severe virulence defect in both nematode and murine models. Further mechanism studies revealed that the mir1Δ/Δ mutant grew more slowly than the wild-type strain and showed severe filamentation defects on the hypha-inducing agar media, including YPD + serum, Lee, Spider + glucose, SLAD, SLD, and YPS. Furthermore, the loss of MIR1 resulted in unfermentable carbon utilisation defect, ATP decrease, and reactive oxygen species (ROS) accumulation in C. albicans. Antioxidant proanthocyanidins, vitamin E, and N-acetyl cysteine (NAC) could reduce intracellular ROS levels and partially rescue the filamentation defects of the mir1Δ/Δ mutant. Accordingly, hypha-specific genes, as well as CEK1 and RIM101 were down-regulated in the mir1Δ/Δ mutant, and this down-regulation could be partially rescued by the addition of the antioxidant NAC. Collectively, MIR1 plays an important role in C. albicans mitochondrial function, filamentation and virulence, and would be a promising antifungal target.https://www.tandfonline.com/doi/10.1080/21501203.2024.2354876Candida albicansMIR1reactive oxygen speciesfilamentationvirulence
spellingShingle Qiao-Ling Hu
Hua Zhong
Xin-Rong Wang
Lei Han
Shan-Shan Ma
Ling Li
Yan Wang
Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
Mycology
Candida albicans
MIR1
reactive oxygen species
filamentation
virulence
title Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
title_full Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
title_fullStr Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
title_full_unstemmed Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
title_short Mitochondrial phosphate carrier plays an important role in virulence of Candida albicans
title_sort mitochondrial phosphate carrier plays an important role in virulence of candida albicans
topic Candida albicans
MIR1
reactive oxygen species
filamentation
virulence
url https://www.tandfonline.com/doi/10.1080/21501203.2024.2354876
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