To understand the role of phospholipids on Cdr1p (drug exporter)-mediated drug resistance in yeast, the phospholipids biosynthesis genes PSD1, PSD2, CHO2, and OPI3 were deleted in a strain of Saccharomyces cerevisiae already overexpressing Cdr1-GFP of Candida albicans as a heterologous system. The effect of phospholipids biosynthesis gene deletion was analyzed on Cdr1p-GFP-mediated drug resistance as well as its localization. The results indicate that phospholipids biosynthesis disruption makes the cell sensitive to several drugs including fluconazole (FLC), with Δpsd1/Cdr1-GFP being worst affected. Interestingly, unlike sterols and sphingolipids, the localization of Cdr1p was unaffected by phospholipid biosynthesis gene disruption. Concomitantly, phospholipids mutants also showed an increase in reactive oxygen species (ROS) generation, as verified by fluorescence probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method. In addition, the sensitivity of phospholipid mutants with FLC was found to be synergistic to ROS generation, resulting in further reduction of growth. Thus, this study proposes phospholipid biosynthesis as a novel target for antifungal therapy.

• Keywords
• Antifungals, Azoles, Candida albicans, Drug resistance, Heterologous expression, Mitochondria, Overexpression, Phospholipids, ROS, pABC3,
• MeSH
• ATP-Binding Cassette Transporters genetics   MeSH
• Antifungal Agents pharmacology   MeSH
• Biosynthetic Pathways MeSH
• Candida albicans drug effects   genetics   MeSH
• Gene Deletion MeSH
• Phosphatidylethanolamine N-Methyltransferase genetics   MeSH
• Phospholipids biosynthesis   MeSH
• Fungal Proteins genetics   MeSH
• Carboxy-Lyases genetics   MeSH
• Membrane Transport Proteins genetics   MeSH
• Microbial Sensitivity Tests MeSH
• Mitochondrial Proteins genetics   MeSH
• Drug Resistance, Multiple, Fungal genetics   MeSH
• Saccharomyces cerevisiae Proteins genetics   MeSH
• Saccharomyces cerevisiae genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ATP-Binding Cassette Transporters MeSH
• Antifungal Agents MeSH
• cdr1 protein, S cerevisiae MeSH Browser
• CHO2 protein, S cerevisiae MeSH Browser
• Phosphatidylethanolamine N-Methyltransferase MeSH
• Phospholipids MeSH
• Fungal Proteins MeSH
• Carboxy-Lyases MeSH
• Membrane Transport Proteins MeSH
• Mitochondrial Proteins MeSH
• Psd1 protein, S cerevisiae MeSH Browser
• Saccharomyces cerevisiae Proteins MeSH

This review summarizes the main results obtained in the fields of general and molecular microbiology and microbial genetics at the Institute of Microbiology of the Academy of Sciences of the Czech Republic (AS CR) [formerly Czechoslovak Academy of Sciences (CAS)] over more than 50 years. Contribution of the founder of the Institute, academician Ivan Málek, to the introduction of these topics into the scientific program of the Institute of Microbiology and to further development of these studies is also included.

• MeSH
• Academies and Institutes history   MeSH
• History, 20th Century MeSH
• Genetics, Microbial history   MeSH
• Molecular Biology history   MeSH
• Check Tag
• History, 20th Century MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH