Carbohydrate metabolism in Brugia pahangi (Nematoda: Filarioidea)

Barrett, John; Mendis, A.H.W.; Butterworth, Penelope E.

doi:10.1016/0020-7519(86)90081-0

Cited by 33 publications

(12 citation statements)

References 14 publications

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“…A closer look at individual metabolic genes indicated a highly specific induction among the key components of anaerobic mitochondrial pathways, such as phosphoenolpyruvate carboxykinase (GenBank:Bm1_25195), malic enzyme/malate dehydrogenase (GenBank:Bm1_04060, GenBank:Bm1_08150, GenBank:Bm1_46465, GenBank:Bm1_53540), and pyruvate dehydrogenase (GenBank:Bm1_26945) [64], [65]. Adult filarial worms are homolactate fermenters that primarily produce lactate via cytosolic pathways when glucose is in excess [66]. Our data suggested that anaerobic mitochondrial metabolism involving malate dismutation is likely activated during parasite development in the mosquito, increasing the total yield of ATP per mole of glucose metabolized.…”

Section: Resultsmentioning

confidence: 99%

Dual RNA-seq of Parasite and Host Reveals Gene Expression Dynamics during Filarial Worm–Mosquito Interactions

et al. 2014

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BackgroundParasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners involved. Here, we conducted a dual RNA-seq time course analysis of filarial worm parasite and host mosquito to better understand the parasite processes underlying development in and interaction with the host tissue, from the establishment of infection to the development of infective-stage larva.Methodology/Principal FindingsUsing the Brugia malayi–Aedes aegypti system, we report parasite gene transcription dynamics, which exhibited a highly ordered developmental program consisting of a series of cyclical and state-transitioning temporal patterns. In addition, we contextualized these parasite data in relation to the concurrent dynamics of the host transcriptome. Comparative analyses using uninfected tissues and different host strains revealed the influence of parasite development on host gene transcription as well as the influence of the host environment on parasite gene transcription. We also critically evaluated the life-cycle transcriptome of B. malayi by comparing developmental stages in the mosquito relative to those in the mammalian host, providing insight into gene expression changes underpinning the mosquito-borne parasitic lifestyle of this heteroxenous parasite.Conclusions/SignificanceThe data presented herein provide the research community with information to design wet lab experiments and select candidates for future study to more fully dissect the whole set of molecular interactions of both organisms in this mosquito-filarial worm symbiotic relationship. Furthermore, characterization of the transcriptional program over the complete life cycle of the parasite, including stages within the mosquito, could help devise novel targets for control strategies.

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Section: Resultsmentioning

confidence: 99%

Dual RNA-seq of Parasite and Host Reveals Gene Expression Dynamics during Filarial Worm–Mosquito Interactions

et al. 2014

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“…LDH is the most active of the glycolytic enzymes. Using crude extracts, LDH activity has been found to be 1.301 U/mg in Brugia pahangi (Barrett et al 1986), 3.613 U/mg in Chandlerella hawkingi (Srivastava and Ghatak 1971), 2.75 U/mg in Setaria cervi (Anwar et al 1977), 6.9 U/mg in Onchocerca volvulus (Walter and Schulz-Key 1980), and 3.097 U/mg in female Molinema dessetae. In previous work we have demonstrated that five isoenzymes are responsible for LDH activity in female M. dessetae (Marchat et al 1994).…”

Section: Discussionmentioning

confidence: 99%

“…27) system to lactate, which is excreted by the worm and metabolized by the host. Amino acids and, especially, glutamine also play a role as energy substrates, providing tricarboxylic-acid-cycle intermediates (Barrett 1981;Köhler 1991;Tielens 1994). Few enzymes involved in carbohydrate metabolism have thus far been considered as targets for chemotherapeutic attack (Wang 1983;Ginger 1991).…”

Section: Introductionmentioning

confidence: 99%

Purification and characterization of lactate dehydrogenase isoenzymes 1 and 2 from Molinema dessetae (Nematoda: Filarioidea)

Marchat

Loiseau

Petek

1996

Parasitology Research

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High levels of lactate dehydrogenase (LDH; EC 1. 1. 1. 27) activity have been detected in the filarial worm Molinema dessetae. The two major LDH isoenzymes (LDH1 and LDH2) from female worms were purified by successive chromatography on diethylaminoethyl (DEAE)-Sepharose, carboxymethyl (CM)-Sepharose, and hydroxyapatite columns followed by fast protein liquid chromatography (FPLC)-gel filtration. LDH1 and LDH2 isoenzymes were found to be dimers with subunits of 58 kDa. They had similar properties with regard to substrate and coenzyme affinity. The apparent Michaelis constants (K(m) values; mean +/- SEM, n = 10) were 0.34 +/- 0.04 mM for pyruvate, 0.25 +/- 0.02 mM for reduced nicotinamide adenine dinucleotide (NADH), 2.5 +/- 0.21 mM for lactate, and 0.18 +/- 0.02 mM for NAD, which suggested that pyruvate reduction was the favored reaction. LDH1 and LDH2 were affected by p-chloromercuribenzoate and Hg2+, and such inhibitory effects could be reversed by the addition of thiol compounds (L-cysteine or beta-mercaptoethanol) as observed for mammalian LDH. Oxalate acted as a noncompetitive inhibitor of pyruvate reduction (Ki = 4.7 +/- 0.35 mM; mean +/- SEM, n = 10) and as a competitive inhibitor with lactate (Ki = 2.3 +/- 0.21 mM), whereas oxamate acted as a competitive inhibitor with pyruvate (Ki = 3.3 +/- 0.28 mM) and was noncompetitive with lactate (Ki = 19 +/- 1.2 mM). These substrate analogues exerted similar effects on mammalian LDH, but the inhibition constants were significantly different. The existence of structural and kinetic differences between mammal and filarial LDH isoenzymes prompted us to evaluate them as targets for chemotherapeutic attack.

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“…Biochemically, mitochondrial GPDH has been reported from adult filarial worms, including Brugia pahangi and Onchocerca spp. (Barrett et al 1986;Dunn et al 1988).…”

Section: Discussionmentioning

confidence: 99%

“…As compared with the glycolytic enzymes, the activities of the TCA-cycle enzymes in filariae have been reported to be low (Barrett 1983;Barrett et al 1986;Comley and Mendis 1986;Dunn et al 1988). In O. fasciata, the hypodermis, body-wall muscle, and reproductive tissues showed moderate to strong localization of the TCAcycle enzymes examined, ICDH [NAD+(P)] and MDH [NAD + (P)].…”

Section: Discussionmentioning

confidence: 99%

Onchocerca fasciata: Enzyme histochemistry and tissue distribution of various dehydrogenases in the adult female worm

1996

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Histochemistry studies of key dehydrogenases in the glycolytic pathway and related enzymes and the tricarboxylic acid (TCA)-cycle enzymes were carried out on adult female Onchocerca fasciata. The distribution pattern and enzymatic activities of 6-phosphogluconate dehydrogenase (6-GPDH), lactate dehydrogenase (LDH), mitochondrial glycerol-3-phosphate dehydrogenase (GPDH), nicotinamide adenine dinucleotide (phosphate) [NAD+(P)]-linked isocitrate dehydrogenase (ICDH), and NAD+(P)-linked malate dehydrogenase (MDH) in various tissues of the worm were determined. Moderate to intense enzyme activities were localized in three main areas, namely, the hypodermis, body-wall muscle, and reproductive tissues. Activity of the formazan reaction product was very low, if at all present, in the intestinal epithelium and was completely absent in the cuticle. On the basis of the present results and earlier observations, it is suggested that glycolysis leading to the end product lactate is the main energy-generating pathway in O. fasciata. The presence of significant activity of 6-GPDH indicates that the pentose-phosphate pathway might be operative in O. fasciata. In light of the activity of some of the TCA-cycle enzymes, ICDH and MDH, demonstrable in O. fasciata, it is possible that an additional pathway (pyruvate-succinate) of glucose metabolism via a reverse sequence of the TCA cycle may also be operative in the worm. The possible functional significance of the enzymes detected is discussed with respect to their location.

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Carbohydrate metabolism in Brugia pahangi (Nematoda: Filarioidea)

Cited by 33 publications

References 14 publications

Dual RNA-seq of Parasite and Host Reveals Gene Expression Dynamics during Filarial Worm–Mosquito Interactions

Dual RNA-seq of Parasite and Host Reveals Gene Expression Dynamics during Filarial Worm–Mosquito Interactions

Purification and characterization of lactate dehydrogenase isoenzymes 1 and 2 from Molinema dessetae (Nematoda: Filarioidea)

Onchocerca fasciata: Enzyme histochemistry and tissue distribution of various dehydrogenases in the adult female worm

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