基于质谱的脂质组学揭示了白色念珠菌脂质稳态与铁获取之间的密切联系。

IF 1.8 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lipids Pub Date : 2025-06-30 DOI:10.1002/lipd.12455
Sana Akhtar Usmani, Khushboo Arya, Basharat Ali, Shikha Chandra, Saumya Chaturvedi, Divyanshi Srivastava, Kunal Khanna, Nitin Bhardwaj, Rajendra Prasad, Ashutosh Singh
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引用次数: 0

摘要

铁是白色念珠菌耐药发展的关键决定因素。一些对铁获取、运输和调控至关重要的基因已经被研究过。先前的研究表明,在铁限制的培养基中生长会改变白色念珠菌细胞的脂质组成。在本研究中,我们对两种主要的铁获取途径蛋白进行了质谱分析:铁转运蛋白Ftr1(亚铁渗透酶)和紧密相连的铜转运蛋白Ccc2。FTR1或CCC2的缺失会导致白色念珠菌的脂质谱发生显著变化,尤其是磷脂和鞘脂代谢。例如,Δftr1和Δccc2突变体鞘脂和甾酯含量均减少,但DAG和TAG含量变化不大。Δccc2细胞的磷脂谱非常独特,PG含量显著升高。Δftr1的总体磷脂谱与野生型差异不大。Δftr1和Δccc2细胞的分子脂质组成有显著差异。这些脂质扰动与Δftr1和Δccc2突变体对靶向脂质生物发生和铁获取的药物的敏感反应相关。综上所述,本研究表明,铁通路蛋白如Ftr1和Ccc2与白色念珠菌的脂质代谢和铁获取密切相关。了解这种脂质-铁结合的机制将有助于探索铁摄取机制和设计联合药物治疗的两种途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mass Spectrometry-Based Lipidomics Reveals a Strong Connection Between Lipid Homeostasis and Iron Acquisition in Candida albicans.

Iron is a critical determinant in the development of drug tolerance in Candida albicans. Several genes essential for iron acquisition, transport, and regulation have been studied. Previous studies have shown that growth in an iron-limited medium alters the lipid compositions of C. albicans cells. In the present study, we performed a mass spectrometry-based lipid analysis of two major iron acquisition pathway proteins: an iron transporter, Ftr1 (ferrous permease), and a closely linked copper transporter, Ccc2. Deletions of FTR1 or CCC2 lead to significant changes in the lipid profile of C. albicans, especially the phospholipid and sphingolipid metabolism. For example, both Δftr1 and Δccc2 mutants showed depleted sphingolipid and steryl ester contents, but not much change in their DAG and TAG contents. The phospholipid profile of Δccc2 cells was quite unique with a much elevated PG content. The overall phospholipid profile of Δftr1 was not much different from the wild type. Both Δftr1 and Δccc2 cells showed significant differences in their molecular lipid species compositions. These lipid perturbations correlated with the susceptible response towards the drugs targeting lipid biogenesis and iron acquisition in Δftr1 and Δccc2 mutants. Taken together, this study shows that iron pathway proteins such as Ftr1 and Ccc2 are closely linked to lipid metabolism and iron acquisition in C. albicans. Understanding the mechanism of this lipid-iron association should be useful in exploring the two pathways for understanding the mechanism of iron uptake and designing the combinatorial drug therapies.

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来源期刊
Lipids
Lipids 生物-生化与分子生物学
CiteScore
4.20
自引率
5.30%
发文量
33
审稿时长
4-8 weeks
期刊介绍: Lipids is a journal of the American Oil Chemists'' Society (AOCS) that focuses on publishing high-quality peer-reviewed papers and invited reviews in the general area of lipid research, including chemistry, biochemistry, clinical nutrition, and metabolism. In addition, Lipids publishes papers establishing novel methods for addressing research questions in the field of lipid research.
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