Abstract:
:Cryptosporidium spp. are the causative agents of diarrheal disease worldwide, but effective treatments are lacking. Cryptosporidium employs mucin-like glycoproteins with O-glycans to attach to and infect host intestinal epithelial cells. The Tn antigen (GalNAcα1-Ser/Thr) is an O-glycan essential for these processes, as Tn-specific lectins and a Tn-specific monoclonal antibody block attachment to and infection of host cells in vitro. The enzymes in Cryptosporidium catalyzing their synthesis, however, have not been studied. Previously, we identified four genes encoding putative UDP N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) in the genomes of three Cryptosporidium spp. Here we report the in silico analysis, cloning, expression, purification, and characterization of one of the four enzymes Cryptosporidium parvum (Cp)-ppGalNAc-T4. This enzyme contains the characteristic domains and motifs conserved in ppGalNAc-Ts and is expressed at multiple time points during in vitro infection. Recombinant soluble Cp-ppGalNAc-T4 was enzymatically active against an unmodified EA2 peptide suggesting that it may function as an "initiating" ppGalNAc-T. Cp-ppGalNAc-T4 also exhibited a strong preference for UDP-GalNAc over other nucleotide sugar donors and was active against unmodified and O-glycosylated versions of the C. parvum gp40-derived peptide, with a preference for the former, suggesting it may play a role in modifying this glycoprotein in vivo. Given the importance of mucin-type O-glycosylation in Cryptosporidium spp., the enzymes that catalyze their synthesis may serve as potential therapeutic targets.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
DeCicco RePass MA,Bhat N,Heimburg-Molinaro J,Bunnell S,Cummings RD,Ward HDdoi
10.1016/j.molbiopara.2018.03.002subject
Has Abstractpub_date
2018-04-01 00:00:00pages
56-65eissn
0166-6851issn
1872-9428pii
S0166-6851(18)30058-6journal_volume
221pub_type
杂志文章abstract::Cryptosporidium spp. are intracellular apicomplexan parasites that cause outbreaks of waterborne diarrheal disease worldwide. Previous studies had identified a Cryptosporidium parvum sporozoite antigen, CpMuc4, that appeared to be involved in attachment and invasion of the parasite into intestinal epithelial cells. Cp...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2014.03.005
更新日期:2014-02-01 00:00:00
abstract::The anaerobic, parasitic protist, Trichomonas vaginalis, is characterized by the absence of mitochondria and the presence of double membrane bound organelles called hydrogenosomes. Succinyl-coenzyme A synthetase is a hydrogenosomal enzyme which catalyzes the formation of ATP via substrate-level phosphorylation. We hav...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(94)90157-0
更新日期:1994-08-01 00:00:00
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
doi:10.1016/0166-6851(94)00200-7
更新日期:1995-02-01 00:00:00
abstract::Over the last years an expanding family of small RNAs (i.e. microRNAs, siRNAs and piRNAs) was recognized as key players in diverse forms of gene silencing and chromatin organization. Effectors functions of these small RNAs are achieved through ribonucleoprotein (RNP) complexes containing at their center an Argonaute/P...
journal_title:Molecular and biochemical parasitology
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doi:10.1016/j.molbiopara.2010.02.003
更新日期:2010-06-01 00:00:00
abstract::The glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) of Trypanosoma brucei is the most abundant GPI-anchored protein expressed on any cell, and is an essential virulence factor. To determine what structural features affect efficient expression of VSG, we made a series of mutations in two ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(03)00055-0
更新日期:2003-05-01 00:00:00
abstract::Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis in humans and animals. To invade host cells, T. gondii deploys the contents of its apically oriented secretory organelles that include the micronemes. Contained within the micronemes are proteins that possess adhesive motifs resembling t...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2003.12.001
更新日期:2004-04-01 00:00:00
abstract::The nucleotide sequence of a gene encoding a 35-kDa thiol protease of the parasitic nematode Haemonchus contortus has been determined. The gene, designated AC-2, shares 97% nucleotide sequence identity and 98% amino acid identity with previously characterized AC-1 cDNAs encoding the thiol protease. The AC-2 gene spans...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(90)90143-a
更新日期:1990-12-01 00:00:00
abstract::Cystic hydatid disease (CHD) is caused by infection with Echinococcus granulosus metacestodes and affects humans and livestock. Proteins secreted or excreted by protoscoleces, pre-adult worms found in the metacestode, are thought to play fundamental roles in the host-parasite relationship. In this work, we performed a...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2012.01.001
更新日期:2012-05-01 00:00:00
abstract::The aspartic protease cathepsin D (Clan AA, Family A1) is expressed in the schistosome gut where it plays an apical role in the digestion of hemoglobin released from ingested erythrocytes. In this report, RNA interference approaches were employed to investigate the effects of knockdown of schistosome cathepsin D. Cult...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2007.10.009
更新日期:2008-02-01 00:00:00
abstract::The physiological role of Schistosomiasis mansoni 22.6 antigen (sm22.6 Ag) and its pathogenic effect on the human host has never been reported. Recombinant sm22.6 Ag is a homogenous polymer under non-denaturing/non-reducing conditions, and an inhibitor to human thrombin. Kinetic and Western blot assays show that the r...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2006.01.012
更新日期:2006-05-01 00:00:00
abstract::In order to clarify the interpretation of molecular karyotype polymorphisms in Leishmania, the three smallest chromosomes from five cloned strains of Leishmania infantum were identified by chromosome-specific anonymous DNA probes. The presence in the same clone of homologous chromosomes of a different size was demonst...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(91)90053-9
更新日期:1991-06-01 00:00:00
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
doi:10.1016/s0166-6851(01)00256-0
更新日期:2001-05-01 00:00:00
abstract::Messenger RNA has been isolated from adults and eggs of Schistosoma mansoni and translated in vitro in mRNA dependent rabbit reticulocyte lysate. The in vitro translation products have been immunoprecipitated using a wide variety of hyperimmune and infection sera from rabbits, mice and humans. A large number of in vit...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(84)90029-x
更新日期:1984-03-01 00:00:00
abstract::Giardia lamblia undergoes surface antigenic variation. The variant-specific surface proteins (VSPs) of isolate WB are cysteine-rich, can vary dramatically in size, contain Cys-X-X-Cys motifs, and are differentially expressed. GS/M(H7) is a Giardia clone from a different isolate which expresses a VSP epitope not found ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(92)90072-r
更新日期:1992-04-01 00:00:00
abstract::An expression vector was constructed to express foreign genes in Trypanosoma congolense. The foreign gene and a neomycin phosphotransferase (NPT) gene are flanked by glutamate and alanine rich protein (GARP) gene processing signals and their expression is driven by a ribosomal RNA gene promoter. The plasmid is not mai...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(99)00136-x
更新日期:1999-10-25 00:00:00
abstract::The presence of virus-derived RNA was investigated in 38 axenically growing Giardia isolates from different geographic areas. The RNA virus was demonstrated in Giardia strains from humans in the U.S.A., England and the majority of strains from Poland. Two strains isolated respectively from a cat and a cavia also conta...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(87)90190-3
更新日期:1987-02-01 00:00:00
abstract::Schistosoma mansoni leucine aminopeptidase (LAP) is thought to play a central role in hatching of the miracidium from the schistosome egg. We identified two discrete LAPs genes in the S. mansoni genome, and their orthologs in S. japonicum. The similarities in sequence and exon/intron structure of the two genes, LAP1 a...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2009.05.002
更新日期:2009-10-01 00:00:00
abstract::Plasmodium falciparum malaria parasites invade human red blood cells and immediately begin making significant alterations to the structure of the erythrocyte. These alterations facilitate the movement of nutrients into, and waste products and parasite-derived proteins out of the cell to meet the needs of the growing p...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章,评审
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更新日期:1996-02-01 00:00:00
abstract::Plasmodium falciparum merozoites invade erythrocytes using a range of alternative ligands that includes erythrocyte binding antigenic proteins (EBAs) and reticulocyte binding protein homologues (Rh). Variation in the expression of some of these genes among culture-adapted parasite lines correlates with the use of diff...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2006.05.014
更新日期:2006-10-01 00:00:00
abstract::We report the isolation and sequence of a part of a gene encoding a collagen from the genome of the human filarial parasite Brugia malayi. The deduced amino acid sequence of the sequenced portion of this gene, which we have designated BmCol1, differs from the most catalogued nematode collagens in that it is composed p...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(91)90027-4
更新日期:1991-03-01 00:00:00
abstract::Both the alpha- and beta-tubulin genes of Leishmania enriettii are encoded by mRNA of 2.0-2.2 kb in length. We have shown previously that the alpha- and beta-tubulin genes are arranged in separate, tandem repeats of 2 and 4 kb, respectively, and now report the mapping of mature mRNA onto these cloned genes. Here we sh...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(85)90029-5
更新日期:1985-04-01 00:00:00
abstract::The Plasmodium MSP-1 is a promising malaria vaccine candidate. However, the highly polymorphic nature of the MSP-1 gene (msp1) presents a potential obstacle for effective vaccine development. To investigate the evolutionary history of msp1 polymorphism in P. vivax, we construct phylogenetic trees of msp1 from P. vivax...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2007.07.002
更新日期:2007-11-01 00:00:00
abstract::Acetylcholinesterase (AChE) plays a key role in postsynaptic transmission in most animals. Nematodes encode multiple AChEs, implying its functional diversity. To explore physiological functions of multiple AChEs, three distinct AChEs (BxACE-1, BxACE-2, and BxACE-3) were identified and characterized from the pinewood n...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2010.11.005
更新日期:2011-02-01 00:00:00
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
doi:10.1016/0166-6851(85)90045-3
更新日期:1985-06-01 00:00:00
abstract::Surface membrane proteins of viable merozoites of Plasmodium chabaudi were iodinated by the Iodogen method and analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Thirteen surface membrane proteins ranging from 22 to 270 kDa were thus identified. Most of these proteins could be immunoprecipitated by...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(84)90014-8
更新日期:1984-01-01 00:00:00
abstract::Root-knot nematodes (Meloidogyne spp.) are among the most important plant pathogens. In this study, the mitochondrial (mt) genomes of the root-knot nematodes, M. chitwoodi and M. incognita were sequenced. PCR analyses suggest that both mt genomes are circular, with an estimated size of 19.7 and 18.6-19.1kb, respective...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2014.04.003
更新日期:2014-03-01 00:00:00
abstract::Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the nuclear factor-kappa B (NF-kappa...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2010.06.005
更新日期:2010-11-01 00:00:00
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
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更新日期:2021-01-07 00:00:00
abstract::Lectins comprise a family of related proteins that mediate essential cell functions through binding to carbohydrates. Within this protein family, C-type lectins are defined by the requirement of calcium for optimal biologic activity. Using reverse transcription PCR, a cDNA corresponding to a putative C-type lectin has...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2006.10.017
更新日期:2007-02-01 00:00:00
abstract::A family of Schistosoma mansoni proteins (18-22 kDa, pI 5.3-5.8) are biosynthesized in juvenile worms and immunoprecipitated by antibodies uniquely present in protective Fischer rat antiserum. A cDNA clone, lambda gt11-40, expressing epitopes common to this protein family was used to obtain a genomic DNA clone, by hyb...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(91)90132-p
更新日期:1991-11-01 00:00:00