Subcellular localization of enzymes of phospholipid metabolism in<i>Candida albicans</i>

Mago, Nandini; Khuller, G. K.

doi:10.1080/02681219080000461

Cited by 12 publications

(7 citation statements)

References 18 publications

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“…PA has been demonstrated to stimulate the activity of phosphatidylinositol-4-phosphate 5-kinase in both mammals and S. cerevisiae ; the resulting accumulation of phosphatidylinositol 4,5-bisphosphate can serve as a focal point for the assembly of cytoskeletal proteins containing pleckstrin homology (PH) domains (Lemmon et al, 1996 ;Tall et al, 1997). In addition, LPA may be generated by the concerted action of PLD1 and a phospholipase A (Mago & Khuller, 1990 ;Goyal & Khuller, 1992), which may act as an inducer of hyphal formation. LPA is known to be a major extracellular signal, produced in large amounts by activated platelets and other cells in human serum, which activates G proteins (Moolenaar, 1995 ;Gaits et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

The role and relevance of phospholipase D1 during growth and dimorphism of Candida albicans

et al. 2001

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The phosphatidylcholine-specific phospholipase D1 (PLD1) in Saccharomyces cerevisiae is involved in vesicle transport and is essential for sporulation. The gene encoding the homologous phospholipase D1 from Candida albicans (PLD1) was used to study the role of PLD1 in this pathogenic fungus. In vitro and in vivo expression studies using Northern blots and reverse transcriptase-PCR showed low PLD1 mRNA levels in defined media supporting yeast growth and during experimental infection, while enhanced levels of PLD1 transcripts were detected during the yeast to hyphal transition. To study the relevance of PLD1 during yeast and hyphal growth, an essential part of the gene was deleted in both alleles of two isogenic strains. In vitro PLD1 activity assays showed that pld1 mutants produced no detectable levels of phosphatidic acid, the hydrolytic product of PLD1 activity, and strongly reduced levels of diacylglycerol, the product of lipid phosphate phosphohydrolase, suggesting no or a negligible background PLD1 activity in the pld1 mutants. The pld1 mutants showed no growth differences compared to the parental wild-type in liquid complex and minimal media, independent of the growth temperature. In addition, growth rates of pld1 mutants in media with protein as the sole source of nitrogen were similar to growth rates of the wild-type, indicating that secretion of proteinases was not reduced. Chlamydospore formation was normal in pld1 mutants. When germ tube formation was induced in liquid media, pld1 mutants showed similar rates of yeast to hyphal transition compared to the wild-type. However, no hyphae formation was observed on solid Spider medium, and cell growth on cornmeal/Tween 80 medium indicated aberrant morphogenesis. In addition, pld1 mutants growing on solid media had an attenuated ability to invade the agar. In a model of oral candidosis, pld1 mutants showed no attenuation of virulence. In contrast, the mutant was less virulent in two different mouse models. These data suggest that PLD1 is not essential for growth and oral infections. However, they also suggest that a prominent part of the phosphatidic acid and diacylglycerol pools is produced by PLD1 and that the level of these components is important for morphological transitions under certain conditions in C. albicans.

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Section: Discussionmentioning

confidence: 99%

The role and relevance of phospholipase D1 during growth and dimorphism of Candida albicans

et al. 2001

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“…Enzyme-Studies in eukaryotic cells have indicated that the kinases involved in the synthesis of the soluble precursors phosphoethanolamine and phosphocholine from ethanolamine and choline, respectively, are localized in the cytosol (21,22). This knowledge led to the assumption that the transmethylation step of the SDPM pathway, catalyzed by Pfpmt, could also occur in the parasite cytoplasm.…”

Section: Pfpmt Is Not a Cytoplasmicmentioning

confidence: 99%

Localization of the Phosphoethanolamine Methyltransferase of the Human Malaria Parasite Plasmodium falciparum to the Golgi Apparatus

Witola

Pessi

Bissati

et al. 2006

Journal of Biological Chemistry

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Phosphatidylcholine is the most abundant phospholipid in the membranes of Plasmodium falciparum, the agent of severe human malaria. The synthesis of this phospholipid occurs via two routes, the CDP-choline pathway, which uses host choline as a precursor, and the plant-like serine decarboxylase-phosphoethanolamine methyltransferase (SDPM) pathway, which uses host serine as a precursor. Although various components of these pathways have been identified, their cellular locations remain unknown. We have previously reported the identification and characterization of the phosphoethanolamine methyltransferase, Pfpmt, of P. falciparum and shown that it plays a critical role in the synthesis of phosphatidylcholine via the SDPM pathway. Here we provide the first evidence that the transmethylation step of the SDPM pathway occurs in the parasite Golgi apparatus. We show that the level of Pfpmt protein in the infected erythrocyte is regulated in a stage-specific fashion, with high levels detected during the trophozoite stage at the peak of parasite membrane biogenesis. Confocal microscopy revealed that Pfpmt is not cytoplasmic. Immunoelectron microscopy revealed that Pfpmt localizes to membrane structures that extend from the nuclear membrane but that it only partially co-localizes with the endoplasmic reticulum marker BiP. Using transgenic parasites expressing green fluorescent protein targeted to different cellular compartments, a complete co-localization was detected with Rab6, a marker of the Golgi apparatus. Together these studies provide the first evidence that the transmethylation step of the SDPM pathway of P. falciparum occurs in the Golgi apparatus and indicate an important role for this organelle in parasite membrane biogenesis.Malaria, the world's most important parasitic disease, is caused by intraerythrocytic protozoan parasites of the genus Plasmodium. More than 300 million clinical cases and more than 2 million deaths are reported each year with most deaths mainly caused by Plasmodium falciparum (1). Unlike other human pathogens that invade metabolically active host cells, P. falciparum invades mature erythrocytes that lack internal organelles and the metabolic pathways necessary for de novo lipid synthesis. During its intraerythrocytic life cycle, P. falciparum undergoes major metabolic and morphological changes and then divides asexually to produce up to 36 new daughter parasites (2). This rapid growth and multiplication requires active synthesis of new membranes and is fueled by lipid precursors derived from the host.Phosphatidylcholine is the major phospholipid in P. falciparum membranes, representing 50% of parasite phospholipids (for review, see Ref.3). Pharmacological studies demonstrated that inhibition of phosphatidylcholine biosynthesis is deleterious to parasite intraerythrocytic growth and multiplication, emphasizing the importance of the phospholipid metabolic pathways as possible targets for development of new antimalarial drugs (4 -10). Recent studies in P. falciparum identified two pathways of...

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“…Investigating the subcellular localization it could be shown that phospholipase A is mostly localized in the microsomal fraction of C. albicans [24].…”

Section: Phospholipase Amentioning

confidence: 99%

“…in 1968 [19] together with phospholipase A. On the subcellular level phospholipase C could be detected in the microsome fraction as well as in the cytosol [24], while it was absent in mitochondria. The maximum activity was found at a pH of 7.5.…”

Section: Phospholipase Cmentioning

confidence: 99%

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Phospholipases of Candida albicans

Niewerth

Körting

2001

Mycoses

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Infections due to Candida albicans are frequent and of clinical importance. Especially at a time of increasing organ transplantations, HIV infections, and resistance to antimicrobial agents a profound knowledge of the interaction between C. albicans and host tissue is mandatory. In addition to secreted aspartyl proteinase, dimorphism, cell surface composition, and toxin production phospholipases are a main factor in pathogenicity. Up to the present, many different groups and subgroups of phospholipases have been detected. These different enzymes are related to various types of aggressive and defensive actions. These range from active invasion of host cell tissue to growth control and remodelling of the yeast cell membrane. It is clear that a multiplicity of factors must co-operate to overcome the host's defences. Yet it can be supposed today that phospholipases are one important factor in this complex interaction. Therefore the known phospholipases of C. albicans are described in detail under clinical aspects.

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Subcellular localization of enzymes of phospholipid metabolism inCandida albicans

Cited by 12 publications

References 18 publications

The role and relevance of phospholipase D1 during growth and dimorphism of Candida albicans

The role and relevance of phospholipase D1 during growth and dimorphism of Candida albicans

Localization of the Phosphoethanolamine Methyltransferase of the Human Malaria Parasite Plasmodium falciparum to the Golgi Apparatus

Phospholipases of Candida albicans

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