3-Methyladenine blocks Toxoplasma gondii division prior to centrosome replication.

Abstract:

:The apicomplexan Toxoplasma gondii replicates by endodyogeny, in which replicated organelles assemble into nascent daughter buds within the maternal parasite. The mechanisms governing this complex sequence are not understood. We now report that the kinase inhibitor 3-methlyadenine (3-MA) efficiently blocks T. gondii replication. The inhibition could not be attributed to the effects of 3-MA on mammalian phosphatidylinositol 3-kinase and host cell autophagy. Furthermore, we show that accumulation of host lysosomes around the parasitophorous vacuoles was unaffected. Most 3-MA-treated parasites failed to form daughter buds or replicate DNA, indicating arrest in G1 or early S-phase. Some 3-MA-treated parasites displayed abortive cell division, in which nuclear segregation to malformed daughter buds was incomplete or asymmetrical. Electron microscopy revealed the presence of residual body-like structures in many vacuoles, even in the absence of daughter buds. Most treated parasites had otherwise normal morphology and were able to resume replication upon drug removal. 3-MA-treated and control parasites were similar with respect to the extent of Golgi body division and apicoplast elongation; however, treated parasites rarely possessed replicated centrosomes or apicoplasts. These data are suggestive of a generalized blockade of T. gondii cell cycle progression at stages preceding centrosome replication, rather than arrest at a specific checkpoint. We hypothesize that 3-MA treatment triggers a cell cycle pause program that may serve to protect parasites during periods, such as subsequent to egress, when cell cycle progression might be deleterious. Elucidation of the mechanism of 3-MA inhibition may provide insight into the control of parasite growth.

journal_name

Mol Biochem Parasitol

authors

Wang Y,Karnataki A,Parsons M,Weiss LM,Orlofsky A

doi

10.1016/j.molbiopara.2010.05.020

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

142-53

issue

2

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(10)00143-X

journal_volume

173

pub_type

杂志文章
  • Conditional removal of selectable markers in Trypanosoma cruzi using a site-specific recombination tool: proof of concept.

    abstract::The scarcity of molecular tools for genetic manipulation is a critical obstacle for functional genomics studies on Trypanosoma cruzi. The current study adapted an inducible site-specific recombination system based on Dimerizable CRE recombinase (DiCRE). Two vectors for stable transfection were created, a first one to ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2015.01.001

    authors: Kangussu-Marcolino MM,Cunha AP,Avila AR,Herman JP,DaRocha WD

    更新日期:2014-12-01 00:00:00

  • Profiling the malaria genome: a gene survey of three species of malaria parasite with comparison to other apicomplexan species.

    abstract::We have undertaken the first comparative pilot gene discovery analysis of approximately 25,000 random genomic and expressed sequence tags (ESTs) from three species of Plasmodium, the infectious agent that causes malaria. A total of 5482 genome survey sequences (GSSs) and 5582 ESTs were generated from mung bean nucleas...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(01)00371-1

    authors: Carlton JM,Muller R,Yowell CA,Fluegge MR,Sturrock KA,Pritt JR,Vargas-Serrato E,Galinski MR,Barnwell JW,Mulder N,Kanapin A,Cawley SE,Hide WA,Dame JB

    更新日期:2001-12-01 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

    doi:10.1016/0166-6851(83)90056-7

    authors: Simon MW,Jayasimhulu K,Mukkada AJ

    更新日期:1983-09-01 00:00:00

  • Identification of a domain of Trypanosoma cruzi metacyclic trypomastigote surface molecule gp82 required for attachment and invasion of mammalian cells.

    abstract::Recombinant proteins and synthetic peptides representing various sequences of gp82, a surface glycoprotein of Trypanosoma cruzi metacyclic trypomastigotes implicated in mammalian cell invasion, were used in this study aiming at the identification of the domain(s) of this molecule required for interaction with target c...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(96)02626-6

    authors: Santori FR,Dorta ML,Juliano L,Juliano MA,da Silveira JF,Ruiz RC,Yoshida N

    更新日期:1996-06-01 00:00:00

  • Trypanosoma brucei MRE11 is non-essential but influences growth, homologous recombination and DNA double-strand break repair.

    abstract::MRE11 is a conserved multi-functional protein that is important for maintaining genomic integrity in yeast and mammalian cells. By database searching, we identified a full-length candidate MRE11 on Trypanosoma brucei chromosome II. We subsequently cloned and sequenced the corresponding gene from the Lister 427 strain....

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(02)00165-2

    authors: Tan KS,Leal ST,Cross GA

    更新日期:2002-11-01 00:00:00

  • Antimalarial action of nitrobenzylthioinosine in combination with purine nucleoside antimetabolites.

    abstract::The infection of human erythrocytes by two strains of the human malarial parasite, Plasmodium falciparum (FCQ-27 or the multi-drug-resistant strain K-1), markedly changed the transport characteristics of the nucleosides, adenosine and tubercidin, compared to uninfected erythrocytes. A component of the transport of the...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(89)90023-6

    authors: Gero AM,Scott HV,O'Sullivan WJ,Christopherson RI

    更新日期:1989-04-01 00:00:00

  • Respiration of Tritrichomonas foetus: components detected in hydrogenosomes and in intact cells by electron paramagnetic resonance spectrometry.

    abstract::Electron paramagnetic resonance spectrometry (EPR) techniques revealed a complex set of redox components in intact respiring cells of Tritrichomonas foetus, an aerotolerant anaerobic protozoon which lacks mitochondria. One of the two main systems of terminal respiration of this organism is the hydrogenosomal system, w...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(80)90047-x

    authors: Ohnishi T,Lloyd D,Lindmark DG,Müller M

    更新日期:1980-10-01 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

    doi:10.1016/0166-6851(88)90030-8

    authors: Ghoda LY,Savarese TM,Northup CH,Parks RE Jr,Garofalo J,Katz L,Ellenbogen BB,Bacchi CJ

    更新日期:1988-01-15 00:00:00

  • Chemiluminescence enhancement by trypanocidal drugs and by inhibitors of antioxidant enzymes in Trypanosoma cruzi.

    abstract::The spontaneous emission of chemiluminescence by Trypanosoma cruzi epimastigotes was 133 +/- 5 counts s-1 (mg protein)-1. The measured intracellular steady state concentration of hydrogen peroxide in the same cells was 1.5 +/- 0.5 microM. These two values are about 12- and 15-times higher than the corresponding ones f...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(88)90093-x

    authors: Giulivi C,Turrens JF,Boveris A

    更新日期:1988-09-01 00:00:00

  • In vitro selection of halofantrine resistance in Plasmodium falciparum is not associated with increased expression of Pgh1.

    abstract::Recent investigations into quinoline and phenanthrene methanol resistance in Plasmodium falciparum have described a linkage between amplification of the mdr homologue pfmdr1 and decreased susceptibility to mefloquine (MQ) and halofantrine (HF). We have examined the current theories on cross-resistance patterns and pfm...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(96)02746-6

    authors: Ritchie GY,Mungthin M,Green JE,Bray PG,Hawley SR,Ward SA

    更新日期:1996-12-02 00:00:00

  • Susceptibility of Plasmodium falciparum cyclic AMP-dependent protein kinase and its mammalian homologue to the inhibitors.

    abstract::Cyclic AMP-dependent protein kinase (protein kinase A, PKA) is a key element in many cell signaling pathways. An essential role of Plasmodium falciparum PKA (PfPKA) activity was reported in the intraerythrocytic growth of the malaria parasite. However, molecular characterization of PfPKA using purified recombinant pro...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2008.03.011

    authors: Sudo A,Kato K,Kobayashi K,Tohya Y,Akashi H

    更新日期:2008-08-01 00:00:00

  • The presence of galactofuranose and ribose units in asparagine-linked oligosaccharides of the digenetic trypanosomatid Endotrypanum schaudinni.

    abstract::It was found that the digenetic trypanosomatid Endotrypanum schaudinni transferred Man7GlcNAc2 in protein N-glycosylation. Endo-beta-N-acetylglucosaminidase H-sensitive oligosaccharides were identified as Man7GlcNAc2, Man6GlcNAc2, Rib1Man6GlcNAc2 and/or Gal1Man6GlcNAc2, Man5GlcNAc containing two galactose or ribose un...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00195-s

    authors: Merello S,Xavier MT,Parodi AJ

    更新日期:1995-01-01 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

    doi:10.1016/s0166-6851(97)00152-7

    authors: Adjé CA,Opperdoes FR,Michels PA

    更新日期:1997-12-01 00:00:00

  • Protection by phospholipids of Schistosoma mansoni schistosomula against the action of cytotoxic antibodies and complement.

    abstract::Schistosoma mansoni schistosomula cultured in the presence of phospholipids showed a decreased sensitivity to the lethal complement-mediated action of anti-schistosome antibodies. Phosphatidyl choline, sphingomyelin and phosphatidyl ethanolamine had a protective action on the schistosomula transformed in vitro by pass...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(87)90002-8

    authors: Billecocq A

    更新日期:1987-09-01 00:00:00

  • Molecular cloning of a myoD-like gene from the parasitic nematode, Trichinella spiralis.

    abstract::The infective larval stage of the nematode Trichinella spiralis is an intracellular parasite of skeletal muscle cells. Infection with T. spiralis results in dedifferentiation of the host cell and the formation of a host/parasite complex. A gene encoding a T. spiralis Helix-Loop-helix (HLH) protein with homology to the...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(96)02673-4

    authors: Connolly B,Trenholme K,Smith DF

    更新日期:1996-10-30 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

    doi:10.1016/j.molbiopara.2009.04.003

    authors: Templeton TJ

    更新日期:2009-08-01 00:00:00

  • PfCG2, a Plasmodium falciparum protein peripherally associated with the parasitophorous vacuolar membrane, is expressed in the period of maximum hemoglobin uptake and digestion by trophozoites.

    abstract::A Plasmodium falciparum gene closely linked to the chloroquine resistance locus encodes PfCG2, a predicted 320-330kDa protein. In the parasitized erythrocyte, PfCG2 expression rises sharply in the trophozoite stage and is detected in electron-dense patches along the parasitophorous vacuolar membrane (PVM), in the cyto...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2005.07.009

    authors: Cooper RA,Papakrivos J,Lane KD,Fujioka H,Lingelbach K,Wellems TE

    更新日期:2005-12-01 00:00:00

  • A unique Rab GTPase, EhRabA, of Entamoeba histolytica, localizes to the leading edge of motile cells.

    abstract::Entamoeba histolytica, an enteric protozoan parasite, infects 10% of the world's population leading to 50 million cases of invasive amoebiasis annually. Parasite vesicle trafficking and motility, which relies on vesicle trafficking to deliver membrane and membrane components to the leading edge, are important for viru...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2004.02.002

    authors: Welter BH,Temesvari LA

    更新日期:2004-06-01 00:00:00

  • Characterization of a polymorphic Theileria annulata surface protein (TaSP) closely related to PIM of Theileria parva: implications for use in diagnostic tests and subunit vaccines.

    abstract::Theileria annulata is a tick-transmitted protozoan that causes tropical theileriosis, an often fatal leukoproliferative disorder of cattle. To characterize and identify parasite proteins suitable as diagnostic antigens and/or vaccine candidates, a cDNA clone encoding a macroschizont stage protein was isolated and char...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(02)00013-0

    authors: Schnittger L,Katzer F,Biermann R,Shayan P,Boguslawski K,McKellar S,Beyer D,Shiels BR,Ahmed JS

    更新日期:2002-04-09 00:00:00

  • Unusual diversity in alpha-amanitin sensitivity of RNA polymerases in trichomonads.

    abstract::Previous studies in the parasitic protist Trichomonas vaginalis have revealed that protein coding genes are transcribed by an alpha-amanitin-resistant RNA polymerase (RNAP) II. To investigate whether this unusual property is a general characteristic of trichomonads, we addressed the physiology of RNA synthesis in lyso...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(01)00294-8

    authors: Vanácová S,Tachezy J,Ullu E,Tschudi C

    更新日期:2001-07-01 00:00:00

  • The cyst wall of Entamoeba invadens contains chitosan (deacetylated chitin).

    abstract::The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen Entamoeba histolytica, contains chitin, which is a homopolymer of beta-1, 4-linked N-acetyl-glucosamine (GlcNAc). In fungi and in bacteria that make nodulation factors, chitin deacetylases make chitosan, which is a mixture of GlcNAc and glucosami...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.03.002

    authors: Das S,Van Dellen K,Bulik D,Magnelli P,Cui J,Head J,Robbins PW,Samuelson J

    更新日期:2006-07-01 00:00:00

  • Optical map of the genotype A1 WB C6 Giardia lamblia genome isolate.

    abstract::The Giardia lamblia genome consists of 12 Mb divided among 5 chromosomes ranging in size from approximately 1 to 4 Mb. The assembled contigs of the genotype A1 isolate, WB, were previously mapped along the 5 chromosomes on the basis of hybridization of plasmid clones representing the contigs to chromosomes separated b...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.07.008

    authors: Perry DA,Morrison HG,Adam RD

    更新日期:2011-12-01 00:00:00

  • Assessment of pfmdr 1 gene copy number by tandem competitive polymerase chain reaction.

    abstract::The pfmdr 1 gene encodes a Plasmodium falciparum homologue of the human P-glycoprotein expressed on the surface of the parasite food vacuole. Variation in copy number and specific codon mutations of pfmdr 1 have been implicated in the development of parasite resistance to antimalarial drugs. We describe here the techn...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(96)02822-8

    authors: Price R,Robinson G,Brockman A,Cowman A,Krishna S

    更新日期:1997-04-01 00:00:00

  • Susceptibility of Plasmodium falciparum to glutamate dehydrogenase inhibitors--a possible new antimalarial target.

    abstract::With the rapid spread of drug-resistant strains of Plasmodium falciparum, the development of new antimalarials is an urgent need. As malaria parasites live in a highly pro-oxidant environment, their anti-oxidant defences have frequently been suggested as candidate drug targets. A key point in such defences is the prod...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2010.04.002

    authors: Aparicio IM,Marín-Menéndez A,Bell A,Engel PC

    更新日期:2010-08-01 00:00:00

  • Purification of an eight subunit RNA polymerase I complex in Trypanosoma brucei.

    abstract::Trypanosoma brucei harbors a unique multifunctional RNA polymerase (pol) I which transcribes, in addition to ribosomal RNA genes, the gene units encoding the major cell surface antigens variant surface glycoprotein and procyclin. In consequence, this RNA pol I is recruited to three structurally different types of prom...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.02.023

    authors: Nguyen TN,Schimanski B,Zahn A,Klumpp B,Günzl A

    更新日期:2006-09-01 00:00:00

  • Molecular epidemiology of giardiasis.

    abstract::Giardia duodenalis is a widespread parasite of mammalian species, including humans. Due to its invariant morphology, investigation on aspects such as host specificity and transmission patterns requires a direct genetic characterization of cysts/trophozoites from host samples. A number of molecular assays have been dev...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审

    doi:10.1016/j.molbiopara.2008.04.006

    authors: Cacciò SM,Ryan U

    更新日期:2008-08-01 00:00:00

  • Distinct effects of HIV protease inhibitors and ERAD inhibitors on zygote to ookinete transition of the malaria parasite.

    abstract::In an effort to eradicate malaria, new interventions are proposed to include compound/vaccine development against pre-erythrocytic, erythrocytic and mosquito stages of Plasmodium. Drug repurposing might be an alternative approach to new antimalarials reducing the cost and the time required for drug development. Previo...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2017.12.003

    authors: Goulielmaki E,Kaforou S,Venugopal K,Loukeris TG,Siden-Kiamos I,Koussis K

    更新日期:2018-03-01 00:00:00

  • Characterization and PCR multiplexing of polymorphic microsatellite loci in the whipworm Trichuris arvicolae, parasite of arvicoline rodents and their cross-species utilization in T. muris, parasite of murines.

    abstract::Trichuris arvicolae and T. muris are gastro-intestinal nematodes of respectively arvicoline and murine rodents. We aim to investigate the ecology of these Trichuris species using population genetics. We sampled nematodes from rodents trapped in the East of France. After confirming the species identification of the nem...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2009.05.007

    authors: Deter J,Galan M,Charbonnel N,Cosson JF

    更新日期:2009-10-01 00:00:00

  • Transient expression of luciferase in Entamoeba histolytica driven by the ferredoxin gene 5' and 3' regions.

    abstract::We have successfully transfected Entamoeba histolytica trophozoites with constructs containing ferredoxin sequences fused to the reporter gene luciferase. We have determined the conditions and parameters necessary to maximise transient luciferase expression in our system. Our optimal construct gave values of 268 x 10(...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(95)02474-3

    authors: Gilchrist CA,Streets HL,Ackers JP,Hall R

    更新日期:1995-10-01 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

    doi:10.1016/s0166-6851(00)00386-8

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

    更新日期:2001-03-01 00:00:00