| The stearoyl-coenzyme A desaturase 1 is essential for virulence and membrane stress in Candida parapsilosis through unsaturated fatty acid production. | |
| | |
MedLine Citation:
|
PMID: 20974817 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Unsaturated fatty acids (UFA) are essential components of cells. In Saccharomyces cerevisiae, stearoyl-coenzyme A (CoA) desaturase 1 (OLE1) affects cell viability through the regulation of oleic (18:1) or palmitoleic (16:1) acid production. In this study, we used a targeted gene deletion approach to determine the impact of OLE1 on the emerging human pathogenic fungus Candida parapsilosis. We found that the deletion of OLE1 resulted in an auxotrophic yeast strain (designated OLE1 KO) that required unsaturated fatty acids for growth but not saturated fatty acids. Additionally, the production of UFA by OLE1 KO yeast cells was markedly reduced, suggesting that Ole1 is essential for UFA production. In contrast to wild-type C. parapsilosis, which produced pseudohyphal growth on UFA-supplemented medium agar, pseudohyphal formation in the OLE1 KO cells was severely impaired, suggesting that Ole1 regulates morphology. Furthermore, the OLE1 KO cells were hypersensitive to various stress-inducing factors, such as salts, SDS, and H(2)O(2), especially at the physiological temperature. The results indicate that OLE1 is essential for the stress response, perhaps through the production of UFA for cell membrane biosynthesis. The OLE1 KO cells also were hypersensitive to human and fetal bovine serum, suggesting that targeting Ole1 could suppress the dissemination of yeast cells in the bloodstream. Murine-like macrophage J774.16 more efficiently killed the OLE1 KO yeasts, and significantly larger amounts of nitric oxide were detected in cocultures of macrophages and OLE1 KO cells than with wild-type or heterozygous strains. Moreover, the disruption of OLE1 significantly reduced fungal virulence in systemic murine infection. Taken together, these results demonstrate that Ole1 regulates the pathobiology of C. parapsilosis via UFA and that the OLE1 pathway is a promising antifungal target. |
| | |
Authors:
|
Long Nam Nguyen; Attila Gacser; Joshua D Nosanchuk |
Related Documents
:
|
9916147 - Sphingomyelins of rat liver: biliary enrichment with molecular species containing 16:0 ... 9767077 - Structure and expression of fatty acid desaturases. 16661107 - Glycerolipid and fatty acid changes in eastern white pine chloroplast lamellae during t... 2072097 - Incorporation of very-long-chain fatty acids into sphingolipids of cultured neural cells. 11028787 - Oxidative cross-linking of pectic polysaccharides from sugar beet pulp. 553937 - Changes in the yield, and carbohydrate, lipid and protein content of milk during lactat... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-25 |
Journal Detail:
|
Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-23 Completed Date: 2011-01-25 Revised Date: 2011-08-01 |
Medline Journal Info:
|
Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
|
Languages: eng Pagination: 136-45 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Ave., New York, New York 10461, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Candida / enzymology*, pathogenicity* Cell Line Cell Membrane / physiology* Fatty Acid Desaturases / genetics, metabolism* Fatty Acids, Unsaturated / metabolism* Gene Deletion Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal / physiology Macrophages / microbiology Mice Phagocytosis Stress, Physiological Virulence |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids, Unsaturated; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.14.99.-/delta-9 fatty acid desaturase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps.
Next Document: Identification of a genetic locus responsible for antimicrobial peptide resistance in Clostridium di...