scholarly journals Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

2006 ◽  
Vol 5 (11) ◽  
pp. 1847-1856 ◽  
Author(s):  
Katarzyna Piekarska ◽  
Els Mol ◽  
Marlene van den Berg ◽  
Guy Hardy ◽  
Janny van den Burg ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Candida Albicans ◽  
Fatty Acid ◽  
Glyoxylate Cycle ◽  
Carbon Sources ◽  
Phagocytic Cells ◽  
Fungal Virulence ◽  
Oxidation Pathway ◽  
Virulence Attenuation ◽  
Peroxisomal Fatty Acid

ABSTRACT Phagocytic cells form the first line of defense against infections by the human fungal pathogen Candida albicans. Recent in vitro gene expression data suggest that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid β-oxidation pathway. Here, we asked whether fatty acid β-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5Δ/pex5Δ mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2Δ/fox2Δ mutant, which lacks the second enzyme of the β-oxidation pathway. Both mutant strains had strongly reduced β-oxidation activity and, accordingly, were unable to grow on media with fatty acids as a sole carbon source. Surprisingly, only the fox2Δ/fox2Δ mutant, and not the pex5Δ/pex5Δ mutant, displayed strong growth defects on nonfermentable carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and showed attenuated virulence in a mouse model for systemic candidiasis. The degree of virulence attenuation of the fox2Δ/fox2Δ mutant was comparable to that of the icl1Δ/icl1Δ mutant, which lacks a functional glyoxylate cycle and also fails to grow on nonfermentable carbon sources. Together, our data suggest that peroxisomal fatty acid β-oxidation is not essential for virulence of C. albicans, implying that the attenuated virulence of the fox2Δ/fox2Δ mutant is largely due to a dysfunctional glyoxylate cycle.

scholarly journals Carnitine-Dependent Transport of Acetyl Coenzyme A in Candida albicans Is Essential for Growth on Nonfermentable Carbon Sources and Contributes to Biofilm Formation

2008 ◽  
Vol 7 (4) ◽  
pp. 610-618 ◽  
Author(s):  
Karin Strijbis ◽  
Carlo W. T. van Roermund ◽  
Wouter F. Visser ◽  
Els C. Mol ◽  
Janny van den Burg ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fatty Acid ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Carbon Sources ◽  
Acetyl Coa ◽  
Oxidation Activity ◽  
Acetyl Coenzyme A ◽  
Human Fungal Pathogen ◽  
Peroxisomal Fatty Acid

ABSTRACT In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid β-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C2 carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid β-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid β-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine dependence may be an important trait of this human fungal pathogen.

scholarly journals Role of Acetyl Coenzyme A Synthesis and Breakdown in Alternative Carbon Source Utilization in Candida albicans

2008 ◽  
Vol 7 (10) ◽  
pp. 1733-1741 ◽  
Author(s):  
Aaron J. Carman ◽  
Slavena Vylkova ◽  
Michael C. Lorenz
Keyword(s):  
Fatty Acids ◽  
Candida Albicans ◽  
Coenzyme A ◽  
Glyoxylate Cycle ◽  
Functional Divergence ◽  
Carbon Sources ◽  
Growth Defect ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme

ABSTRACT Acetyl coenzyme A (acetyl-CoA) is the central intermediate of the pathways required to metabolize nonfermentable carbon sources. Three such pathways, i.e., gluconeogenesis, the glyoxylate cycle, and β-oxidation, are required for full virulence in the fungal pathogen Candida albicans. These processes are compartmentalized in the cytosol, mitochondria, and peroxosomes, necessitating transport of intermediates across intracellular membranes. Acetyl-CoA is trafficked in the form of acetate by the carnitine shuttle, and we hypothesized that the enzymes that convert acetyl-CoA to/from acetate, i.e., acetyl-CoA hydrolase (ACH1) and acetyl-CoA synthetase (ACS1 and ACS2), would regulate alternative carbon utilization and virulence. We show that C. albicans strains depleted for ACS2 are unviable in the presence of most carbon sources, including glucose, acetate, and ethanol; these strains metabolize only fatty acids and glycerol, a substantially more severe phenotype than that of Saccharomyces cerevisiae acs2 mutants. In contrast, deletion of ACS1 confers no phenotype, though it is highly induced in the presence of fatty acids, perhaps explaining why acs2 mutants can utilize fatty acids. Strains lacking ACH1 have a mild growth defect on some carbon sources but are fully virulent in a mouse model of disseminated candidiasis. Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. Together, these results show that acetyl-CoA metabolism and transport are critical for growth of C. albicans on a wide variety of nutrients. Furthermore, the phenotypic differences between mutations in these highly conserved genes in S. cerevisiae and C. albicans support recent findings that significant functional divergence exists even in fundamental metabolic pathways between these related yeasts.

scholarly journals Synthesis of fatty acids in the perfused mouse liver

1974 ◽  
Vol 142 (3) ◽  
pp. 611-618 ◽  
Author(s):  
D. Michael W. Salmon ◽  
Neil L. Bowen ◽  
Douglas A. Hems
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Carbon Sources ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Total Rate ◽  
Glucose Carbon

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of3H from3H2O (1–7μmol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-14C]lactic acid and [U-14C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of3H2O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12–16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with3H2O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

scholarly journals Paucibacter toxinivorans gen. nov., sp. nov., a bacterium that degrades cyclic cyanobacterial hepatotoxins microcystins and nodularin

2005 ◽  
Vol 55 (4) ◽  
pp. 1563-1568 ◽  
Author(s):  
Jarkko Rapala ◽  
Katri A. Berg ◽  
Christina Lyra ◽  
R. Maarit Niemi ◽  
Werner Manz ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Gene Sequence ◽  
Sequence Similarity ◽  
Carbon Sources ◽  
16S Rrna Gene Sequence ◽  
Rrna Gene ◽  
Rrna Gene Sequence

Thirteen bacterial isolates from lake sediment, capable of degrading cyanobacterial hepatotoxins microcystins and nodularin, were characterized by phenotypic, genetic and genomic approaches. Cells of these isolates were Gram-negative, motile by means of a single polar flagellum, oxidase-positive, weakly catalase-positive and rod-shaped. According to phenotypic characteristics (carbon utilization, fatty acid and enzyme activity profiles), the G+C content of the genomic DNA (66·1–68·0 mol%) and 16S rRNA gene sequence analysis (98·9–100 % similarity) the strains formed a single microdiverse genospecies that was most closely related to Roseateles depolymerans (95·7–96·3 % 16S rRNA gene sequence similarity). The isolates assimilated only a few carbon sources. Of the 96 carbon sources tested, Tween 40 was the only one used by all strains. The strains were able to mineralize phosphorus from organic compounds, and they had strong leucine arylamidase and chymotrypsin activities. The cellular fatty acids identified from all strains were C16 : 0 (9·8–19 %) and C17 : 1 ω7c (<1–5·8 %). The other predominant fatty acids comprised three groups: summed feature 3 (<1–2·2 %), which included C14 : 0 3-OH and C16 : 1 iso I, summed feature 4 (54–62 %), which included C16 : 1 ω7c and C15 : 0 iso OH, and summed feature 7 (8·5–28 %), which included ω7c, ω9c and ω12t forms of C18 : 1. A more detailed analysis of two strains indicated that C16 : 1 ω7c was the main fatty acid. The phylogenetic and phenotypic features separating our strains from recognized bacteria support the creation of a novel genus and species, for which the name Paucibacter toxinivorans gen. nov., sp. nov. is proposed. The type strain is 2C20T (=DSM 16998T=HAMBI 2767T=VYH 193597T).

scholarly journals Identification and Characterization of Oleaginous Yeast Isolated from Kefir and Its Ability to Accumulate Intracellular Fats in Deproteinated Potato Wastewater with Different Carbon Sources

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Iwona Gientka ◽  
Marek Kieliszek ◽  
Karolina Jermacz ◽  
Stanisław Błażejak
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fossil Fuels ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Carbon Sources ◽  
Debaryomyces Hansenii ◽  
Industry Waste ◽  
Identification And Characterization

The search for efficient oleaginous microorganisms, which can be an alternative to fossil fuels and biofuels obtained from oilseed crops, has been going on for many years. The suitability of microorganisms in this regard is determined by their ability to biosynthesize lipids with preferred fatty acid profile along with the concurrent utilization of energy-rich industrial waste. In this study, we isolated, characterized, and identified kefir yeast strains using molecular biology techniques. The yeast isolates identified wereCandida inconspicua,Debaryomyces hansenii,Kluyveromyces marxianus,Kazachstania unispora, andZygotorulaspora florentina. We showed that deproteinated potato wastewater, a starch processing industry waste, supplemented with various carbon sources, including lactose and glycerol, is a suitable medium for the growth of yeast, which allows an accumulation of over 20% of lipid substances in its cells. Fatty acid composition primarily depended on the yeast strain and the carbon source used, and, based on our results, most of the strains met the criteria required for the production of biodiesel. In particular, this concerns a significant share of saturated fatty acids, such as C16:0 and C18:0, and unsaturated fatty acids, such as C18:1 and C18:2. The highest efficiency in lipid biosynthesis exceeded 6.3 g L−1.Kazachstania unisporawas able to accumulate the high amount of palmitoleic acid.

Dihomo-gamma-linolenic acid induces fat loss in C. elegans in an omega-3-independent manner by promoting peroxisomal fatty acid β-oxidation

2018 ◽  
Vol 9 (3) ◽  
pp. 1621-1637 ◽  
Author(s):  
David Navarro-Herrera ◽  
Paula Aranaz ◽  
Laura Eder-Azanza ◽  
María Zabala ◽  
Cristina Hurtado ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Omega 3 ◽  
Gamma Linolenic Acid ◽  
Independent Manner ◽  
C Elegans ◽  
Beneficial Effects ◽  
Body Fat Content ◽  
Omega 6 ◽  
Peroxisomal Fatty Acid

Omega-6 fatty acids might induce beneficial effects on body fat-content and metabolism.

Peroxisomal fatty acid α- and β-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases

2001 ◽  
Vol 29 (2) ◽  
pp. 250-267 ◽  
Author(s):  
R. J. A. Wanders ◽  
P. Vreken ◽  
S. Ferdinandusse ◽  
G. A. Jansen ◽  
H. R. Waterham ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Genetic Diseases ◽  
Cellular Metabolism ◽  
Peroxisomal Membrane ◽  
Subcellular Organelles ◽  
Current State ◽  
Peroxisomal Fatty Acid

Peroxisomes are subcellular organelles with an indispensable role in cellular metabolism. The importance of peroxisomes for humans is stressed by the existence of a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. Most of these functions have to do with lipid metabolism including the α and β-oxidation of fatty acids. Here we describe the current state of knowledge about peroxisomal fatty acid α- and β-oxidation with particular emphasis on the following: (1) the substrates β-oxidized in peroxisomes; (2) the enzymology of the α- and β-oxidation systems; (3) the permeability properties of the peroxisomal membrane and the role of the different transporters therein; (4) the interaction with other subcellular compartments, including the mitochondria, which are the ultimate site of NADH reoxidation and full degradation of acetyl-CoA to CO2 and water; and (5) the different disorders of peroxisomal α- and β-oxidation.

scholarly journals Elucidation of carbon sources used for the biosynthesis of fatty acids and sterols in the trypanosomatid Leishmania mexicana

1999 ◽  
Vol 342 (2) ◽  
pp. 397-405 ◽  
Author(s):  
Michael L. GINGER ◽  
Michael L. CHANCE ◽  
L. John GOAD
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Amino Acid ◽  
Acid Production ◽  
Carbon Sources ◽  
Mevalonic Acid ◽  
Leishmania Mexicana ◽  
Fatty Acid Production ◽  
Quantitative Measurements ◽  
Major Sterol

Sterols are necessary for the growth of trypanosomatid protozoans; sterol biosynthesis is a potential target for the use and development of drugs to treat the diseases caused by these organisms. This study has used 14C-labelled substrates to investigate the carbon sources utilized by promastigotes and amastigotes of Leishmania mexicana for the production of sterol [mainly ergosta-5,7,24(241)-trien-3β-ol] and the fatty acid moieties of the triacylglycerol (TAG) and phospholipid (PL) of the organism. The isoprenoid precursor mevalonic acid (MVA) was incorporated into the sterols, and the sterol precursor squalene, by the promastigotes of L. mexicana. However, acetate (the precursor to MVA in most organisms) was a very poor substrate for sterol production but was readily incorporated into the fatty acids of TAG and PL. Other substrates (glucose, palmitic acid, alanine, serine and isoleucine), which are metabolized to acetyl-CoA, were also very poor precursors to sterol but were incorporated into TAG and PL and gave labelling patterns of the lipids similar to those of acetate. In contrast, the amino acid leucine was the only substrate to be incorporated efficiently into the squalene and sterol of L. mexicana promastigotes. Quantitative measurements revealed that at least 70-80% of the sterol synthesized by the promastigotes of L. mexicana is produced from carbon provided by leucine metabolism. Studies with the amastigote form of L. mexicana showed that in this case leucine was again the major sterol precursor, whereas acetate was utilized for fatty acid production.

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