Autophagy in parasitic protists: unique features and drug targets.


:Eukaryotic cells can degrade their own components, cytosolic proteins and organelles, using dedicated hydrolases contained within the acidic interior of their lysosomes. This degradative process, called autophagy, is used under starvation conditions to recycle redundant or less important macromolecules, facilitates metabolic re-modeling in response to environmental cues, and is also often important during cell differentiation. In this review, we discuss the role played by autophagy during the life cycles of the major parasitic protists. To provide context, we also provide an overview of the different forms of autophagy and the successive steps in the autophagic processes, including the proteins involved, as revealed in recent decades by studies using the model organism Saccharomyces cerevisiae, methylotrophic yeasts and mammalian cells. We describe for trypanosomatid parasites how autophagy plays a role in the differentiation from one life cycle stage to the next one and, in the case of the intracellular parasites, for virulence. For malarial parasites, although only a limited repertoire of canonical autophagy-related proteins can be detected, autophagy seems to play a role in the removal of redundant organelles important for cell invasion, when sporozoites develop into intracellular trophozoites inside the hepatocytes. The complete absence of a canonical autophagy pathway from the microaerophile Giardia lamblia is also discussed. Finally, the essential role of autophagy for differentiation and pathogenicity of some pathogenic protists suggests that the proteins involved in this process may represent new targets for drug development. Opportunities and strategies for drug design targeting autophagy proteins are discussed.


Mol Biochem Parasitol


Brennand A,Gualdrón-López M,Coppens I,Rigden DJ,Ginger ML,Michels PA




Has Abstract


2011-06-01 00:00:00














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    abstract::The glycoproteins of 12-28 kD from Taenia solium metacestodes provide a high specificity and sensitivity for the serological diagnosis of the central nervous system infection, neurocysticercosis. Their widespread use as antigens for routine serological assays will require their production in large and reproducible amo...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Obregón-Henao A,Gil DL,Gómez DI,Sanzón F,Teale JM,Restrepo BI

    更新日期:2001-05-01 00:00:00

  • Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach.

    abstract::Parasitic infections are a widespread health problem and research of novel anthelmintic compounds is of the utmost importance. In this study we performed a virtual screening campaign by coupling ligand-based pharmacophore, homology modeling and molecular docking. The virtual screening campaign was conducted using a jo...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Stevanovic S,Marjanović DS,Trailović SM,Zdravković N,Perdih A,Nikolic K

    更新日期:2021-01-07 00:00:00

  • Cloning and characterization of the ribosomal RNA gene repeat from Ostertagia ostertagi.

    abstract::Clones of the rRNA genes of Ostertagia ostertagi were selected from a library prepared from the genomic DNA of adult worms of strain LA-2. A 13.4-kb insert in a clone, lambda OOR78, is comprised of one complete 7.5-kb rDNA unit and portions of two adjacent units. The rDNA unit is directly repeated in a head-to-tail fa...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Dame JB,Yowell CA,Courtney CH,Lindgren WG

    更新日期:1991-04-01 00:00:00

  • The role of aminopeptidases in haemoglobin degradation in Plasmodium falciparum-infected erythrocytes.

    abstract::Intra-erythrocytic Plasmodium parasites digest host cell haemoglobin and use the liberated amino acids for protein synthesis. Although several endoproteases (aspartic, cysteine, and metallo-) have been shown to be involved in the initial stages of haemoglobin degradation, little is known about the steps immediately be...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Gavigan CS,Dalton JP,Bell A

    更新日期:2001-09-28 00:00:00

  • The fate of ferriprotorphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs.

    abstract::The intraerythrocytic malaria parasite digests considerable amounts of its host cell cytosol, which consists mostly of hemoglobin. In order to avert the toxicity of ferriprotorphyrin IX (FP) thus produced, it is generally accepted that FP is polymerized to the non-toxic hemozoin. Investigating the fate of FP in cultur...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Zhang J,Krugliak M,Ginsburg H

    更新日期:1999-03-15 00:00:00

  • The complete sequence of a Plasmodium malariae SSUrRNA gene and its comparison to other plasmodial SSUrRNA genes.

    abstract::A gene encoding the small subunit rRNA (SSUrRNA) has been isolated from the human parasite, Plasmodium malariae. The gene has been sequenced. It contains conserved and variable regions which conform to patterns established for other eukaryotic SSUrRNA genes. Comparisons with other SSUrRNA genes from Plasmodium species...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


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    更新日期:1991-04-01 00:00:00

  • Properties of the acid thiol proteinase from Schistosoma mansoni adults.

    abstract::Seven beta-naphthylamine-linked peptides were tested as substrates for a previously described thiol proteinase of adult Schistosoma mansoni. The enzyme was not active on carbobenoxy-arginyl-arginyl-4-methoxy-2-naphthylamide and carbobenzoxy-alanyl-arginyl-arginyl-4-methoxy-2-naphthylamide. Enzyme activity was maximal ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


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    更新日期:1981-11-01 00:00:00

  • Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells.

    abstract::The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the o...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


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  • Comparative biochemical and functional properties of two leucine aminopeptidases of Clonorchis sinensis.

    abstract::Leucine aminopeptidases (LAP; EC are a group of metalloexopeptidases, which catalyze the sequential removal of leucine amino acids from the N-termini of the polypeptides or proteins. In this study, we identified two novel genes that encode LAPs of Clonorchis sinensis (CsLAP1 and CsLAP2) and characterized the...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Kang JM,Ju HL,Ju JW,Sohn WM,Kim TS,Bahk YY,Hong SJ,Na BK

    更新日期:2012-03-01 00:00:00

  • Analysis of the sequences flanking the translational start sites of Plasmodium falciparum.

    abstract::The 5' and 3' regions adjacent to the initiation codon in 22 Plasmodium falciparum sequences were examined. A 5' consensus sequence (AAAA/ATG) was found. Although P. falciparum non-translated DNA is A-rich, A occurred significantly more frequently in the 4 positions preceding the initiation ATG than in adjacent non-tr...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Saul A,Battistutta D

    更新日期:1990-08-01 00:00:00

  • Characterisation of protein kinase C like activities in Trypanosoma brucei.

    abstract::Protein kinase activities in bloodstream and procyclic forms of Trypanosoma brucei have been partially purified and characterised. Cytosolic extracts were separated on DEAE-cellulose and assayed for the ability to phosphorylate histone in the presence of Ca2+ and diacylglycerol. Five peaks of activity were identified ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Keith K,Hide G,Tait A

    更新日期:1990-11-01 00:00:00

  • Genetic and antigenic characterization of Babesia bovis merozoite spherical body protein Bb-1.

    abstract::A Babesia bovis merozoite protein, Bb-1, was localized by immunoelectron microscopy to an apical organelle known as the spherical body. This unique structure appears to be analogous to dense granules of other apicomplexan protozoa. Similar to previously described dense granule proteins of Plasmodium spp., Bb-1 is secr...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Hines SA,Palmer GH,Brown WC,McElwain TF,Suarez CE,Vidotto O,Rice-Ficht AC

    更新日期:1995-02-01 00:00:00

  • Sequences with high propensity to form G-quartet structures in kinetoplast DNA from Phytomonas serpens.

    abstract::Naturally occurring sequences containing repetitive guanine motifs have the potential to form tetraplex DNA. Phytomonas serpens minicircle DNA shows some regions where one strand is composed mainly of G and T (GT regions). These regions contain several stretches of contiguous guanines. An oligonucleotide was construct...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Sá-Carvalho D,Traub-Cseko YM

    更新日期:1995-06-01 00:00:00

  • L-myo-Inositol 1-phosphate synthase from Entamoeba histolytica.

    abstract::L-myo-Inositol 1-phosphate synthase (I-1-P synthase) catalyses the primary reaction for the synthesis of inositol in a variety of prokaryotes, eukaryotes and in the chloroplasts of algae and higher plants. Inositol is a precursor of essential macromolecules like membrane phospholipids, GPI anchor proteins and lipophos...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Lohia A,Hait NC,Majumder AL

    更新日期:1999-01-05 00:00:00

  • The two mechanisms for antigenic variation in Trypanosoma brucei are independent processes.

    abstract::Antigenic switching in Trypanosoma brucei can occur either by the production of a telomeric copy of a variant surface glycoprotein (VSG) gene through a gene conversion mechanism or by the nonduplicative activation of a telomeric VSG gene. The 5 VSG gene telomeric copy that is expressed in IsTaR 1 variant antigenic typ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Aline RF Jr,Stuart K

    更新日期:1985-06-01 00:00:00

  • A comparison of the enzymatic properties of the major cysteine proteinases from Trypanosoma congolense and Trypanosoma cruzi.

    abstract::Congopain and cruzipain, the major cysteine proteinases from Trypanosoma congolense and Trypanosoma cruzi, were compared for their activities towards a series of new, sensitive fluorogenic substrates of the papain family of cysteine proteinases and for their sensitivity to inhibition by cystatins and related biotinyla...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Chagas JR,Authie E,Serveau C,Lalmanach G,Juliano L,Gauthier F

    更新日期:1997-09-01 00:00:00

  • The varieties of gene amplification, diversification and hypervariability in the human malaria parasite, Plasmodium falciparum.

    abstract::The human malaria parasite, Plasmodium falciparum, is able to evade host cell-mediated and humoral immunity to maintain both persistent and repeated infections. Immune evasion is in part due to a robust repertoire of proteins which participate in host-parasite interactions but also exhibit profound antigenic diversity...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审


    authors: Templeton TJ

    更新日期:2009-08-01 00:00:00

  • Microarray based analysis of temperature and oxidative stress induced messenger RNA in Schistosoma mansoni.

    abstract::The body's defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host i...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Aragon AD,Imani RA,Blackburn VR,Cunningham C

    更新日期:2008-12-01 00:00:00

  • Characterization of macromolecular transport pathways in malaria-infected erythrocytes.

    abstract::We have previously provided evidence for a pathway in Plasmodium falciparum-infected erythrocytes, coined the parasitophorous duct pathway, which provides serum (macro)molecules direct access to intraerythrocytic parasites . The present study addresses the purity of the fluorescent macromolecules used to define the du...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Goodyer ID,Pouvelle B,Schneider TG,Trelka DP,Taraschi TF

    更新日期:1997-07-01 00:00:00

  • A Plasmodium falciparum isolate with a chromosome 9 deletion expresses a trypsin-resistant cytoadherence molecule.

    abstract::Sequestration of Plasmodium falciparum infected erythrocytes in the cerebral circulation is strongly implicated in the pathogenesis of cerebral malaria. From previous studies it was postulated that genes essential for cytoadherence were located on the right arm of chromosome 9 as P. falciparum isolates with a deletion...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Chaiyaroj SC,Coppel RL,Magowan C,Brown GV

    更新日期:1994-09-01 00:00:00

  • Organization, sequence and stage-specific expression of the phosphoglycerate kinase genes of Leishmania mexicana mexicana.

    abstract::In Leishmania mexicana two genes were detected coding for different isoforms of the glycolytic enzyme phosphoglycerate kinase. This situation contrasts with that observed in other Trypanosomatidae (Trypanosoma brucei, Trypanosoma congolense, Crithidia fasciculata) analyzed previously, which all contain three different...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Adjé CA,Opperdoes FR,Michels PA

    更新日期:1997-12-01 00:00:00

  • Purification and characterization of gamma-glutamyl transpeptidase from Ascaris suum.

    abstract::gamma-Glutamyl transpeptidase, which is of central importance in the degradation of glutathione, was purified from Ascaris suum to apparent homogeneity. The enzyme was found to be a predominantly membrane-bound protein and was solubilized by Triton X-100. The purified enzyme, which exhibits a specific activity of 1009...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Hussein AS,Walter RD

    更新日期:1996-04-01 00:00:00

  • Stage-specific expression of the Leishmania mexicana paraflagellar rod protein PFR-2.

    abstract::A screen for Leishmania mexicana genes encoding promastigote-specific flagellar proteins resulted in isolation of genes encoding the major components of the paraflagellar rod. One of these, PFR-2, was characterized extensively. PFR-2 genes are present in the genome as a tandem array of three genes designated PFR-2A, P...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Moore LL,Santrich C,LeBowitz JH

    更新日期:1996-10-01 00:00:00

  • The immunodominant 17-kDa antigen from Cryptosporidium parvum is glycosylphosphatidylinositol-anchored.

    abstract::Cryptosporidium parvum is a protozoan parasite of the intestinal epithelium that has caused numerous outbreaks of diarrheal illness in humans. During our studies of the host immune response to C. parvum infection, we noted that two of the immunodominant surface antigens of the sporozoite stage of the parasite readily ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Priest JW,Xie LT,Arrowood MJ,Lammie PJ

    更新日期:2001-03-01 00:00:00

  • Characterization of phosphodiesterase-5 as a surface protein in the tegument of Schistosoma mansoni.

    abstract::Schistosoma mansoni is a major causative agent of schistosomiasis, an important parasitic disease that constitutes a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection and the development of an effective vaccine still remains the most desirable me...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Rofatto HK,Tararam CA,Borges WC,Wilson RA,Leite LC,Farias LP

    更新日期:2009-07-01 00:00:00

  • Purification and partial characterization of an unusual protein of Plasmodium falciparum: histidine-rich protein II.

    abstract::The human malarial parasite Plasmodium falciparum secretes a histidine-rich protein (HRP-II) from infected erythrocytes. HRP-II has a very high content of histidine (H) (34%), alanine (A) (37%) and aspartic acid (D) (10%) and many contiguous repeats of the sequences AHH and AHHAAD. The histidine content of the protein...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Panton LJ,McPhie P,Maloy WL,Wellems TE,Taylor DW,Howard RJ

    更新日期:1989-06-15 00:00:00

  • Unique kinetic mechanism of Plasmodium falciparum adenylosuccinate synthetase.

    abstract::Adenylosuccinate synthetase (AdSS) catalyses the Mg(2+) dependent formation of adenylosuccinate from IMP and aspartate, the reaction being driven by the hydrolysis of GTP to GDP. All characterized AdSS thus far exhibit a random kinetic mechanism. We present here kinetic evidence that unlike all other AdSS, Plasmodium ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Raman J,Mehrotra S,Anand RP,Balaram H

    更新日期:2004-11-01 00:00:00

  • Karyotype and synteny among the chromosomes of all four species of human malaria parasite.

    abstract::The karyotype and chromosomes of the human malaria parasite Plasmodium falciparum have been well characterized in recent years. Here we present karyotype maps of the three other human malaria species, P. vivax, P. malariae and P. ovale. Chromosomes of these species were found to be of significantly higher molecular we...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Carlton JM,Galinski MR,Barnwell JW,Dame JB

    更新日期:1999-06-25 00:00:00

  • Molecular biology of the hexokinase isoenzyme pattern that distinguishes pathogenic Entamoeba histolytica from nonpathogenic Entamoeba dispar.

    abstract::The electrophoretic patterns of hexokinase and phosphoglucomutase have been widely used to distinguish Entamoeba histolytica from Entamoeba dispar isolates. Although E. histolytica and E. dispar, previously called pathogenic and nonpathogenic Entamoeba histolytica, differ clearly in sequences of many homologous genes,...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Ortner S,Clark CG,Binder M,Scheiner O,Wiedermann G,Duchêne M

    更新日期:1997-05-01 00:00:00

  • The free amino acid pool in Leishmania tropica promastigotes.

    abstract::The principal constituents of the free amino acid pool in Leishmania tropica promastigotes include alanine, glycine, serine, threonine, alpha-aminobutyric acid and ethanolamine. Changes in levels of the pool constituents during starvation, nutrient supplementation and treatment with a metabolic inhibitor (sodium fluor...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Simon MW,Jayasimhulu K,Mukkada AJ

    更新日期:1983-09-01 00:00:00