Abstract：
:Benznidazole is the main drug used to treat Trypanosoma cruzi infections. However, frequent instances of treatment failure have been reported. To better understand potential resistance mechanisms, we analysed three clones isolated from a single parasite population that had undergone benznidazole-selection. These clones exhibited differing levels of benznidazole-resistance (varying between 9 and 26-fold), and displayed cross-resistance to nifurtimox (2 to 4-fold). Each clone had acquired a stop-codon-generating mutation in the gene which encodes the nitroreductase (TcNTR) that is responsible for activating nitroheterocyclic pro-drugs. In addition, one clone had lost a copy of the chromosome containing TcNTR. However, these processes alone are insufficient to account for the extent and diversity of benznidazole-resistance. It is implicit from our results that additional mechanisms must also operate and that T. cruzi has an intrinsic ability to develop drug-resistance by independent sequential steps, even within a single population. This has important implications for drug development strategies.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Campos MC,Leon LL,Taylor MC,Kelly JMdoi
10.1016/j.molbiopara.2014.01.002subject
Has Abstractpub_date
2014-01-01 00:00:00pages
17-9issue
1eissn
0166-6851issn
1872-9428pii
S0166-6851(14)00003-6journal_volume
193pub_type
杂志文章abstract：:Glucose is a major source of energy and carbon in promastigotes of Leishmania mexicana, and its uptake is mediated by three glucose transporters whose genes are encoded within a single cluster. A null mutant in which the glucose transporter gene cluster was deleted by homologous gene replacement was generated previous...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2007.01.010
更新日期：2007-05-01 00:00:00
abstract：:Antibodies raised against a Leishmania major recombinant promastigote surface antigen 2 (PSA-2) fragment recognized three major polypeptides of approximate M(r) 96,000, 80,000 and 50,000 in promastigotes of three Israeli isolates of L. major including the cloned line LRC-L137-V121, but detected a different array of po...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(94)90100-7
更新日期：1994-09-01 00:00:00
abstract：:Entamoeba histolytica is a human intestinal parasite that causes amebic dysentery. A cell surface amebic adhesin, the galactose and N-acetyl-D-galactosamine inhibitable (GalNAc) lectin mediates amebic adherence to and contact-dependent killing of host cells. Previous work has suggested that the GalNAc lectin transduce...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(02)00326-2
更新日期：2003-04-03 00:00:00
abstract：:The expressed sequence tag (EST) dataset of Toxoplasma gondii provides a wealth of information towards gene discovery. The complete cDNA and genomic sequence of EST tgc050 locus shows that it contains five copies of the conserved thrombospondin (TSP)-like motif present in a number of molecules with adhesive properties...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(96)02796-x
更新日期：1997-02-01 00:00:00
abstract：:Cloned DNA fragments of the ribosomal RNA gene of Schistosoma mansoni hybridise strongly to Echinococcus DNA following restriction endonuclease and Southern transfer analysis. Individuals within a strain of E. granulosus exhibit identical patterns of hybridisation. However, the hybridisation patterns show significant ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(85)90016-7
更新日期：1985-11-01 00:00:00
abstract：:Erythrocyte invasion by malaria parasites requires specific receptor-ligand interactions. Plasmodium vivax and Plasmodium knowlesi are completely dependent on binding the Duffy blood group antigen to invade human erythrocytes. P. knowlesi invades rhesus erythrocytes by multiple pathways using the Duffy antigen as well...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(02)00017-8
更新日期：2002-04-30 00:00:00
abstract：:A complex of non-covalently bound polypeptides is located on the surface of the merozoite form of the human malaria parasite Plasmodium falciparum. Four of these polypeptides are derived by proteolytic processing of the merozoite surface protein 1 (MSP-1) precursor. Two components, a 22 and a 36 kDa polypeptide are no...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(00)00350-9
更新日期：2001-01-15 00:00:00
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
doi：10.1016/0166-6851(96)02573-x
更新日期：1996-04-01 00:00:00
abstract：:A wide range of secondary biological functions have been documented for eukaryotic aminoacyl-tRNA synthetases including roles in transcriptional regulation, mitochondrial RNA splicing, cell growth, and chemokine-like activities. The asparaginyl-tRNA synthetase (AsnRS) of the filarial nematode, Brugia malayi, is a high...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2012.06.003
更新日期：2012-09-01 00:00:00
abstract：:It has been shown that vaccination with two low molecular mass excretory secretory (ES) antigens of 15 and 24 kDa, respectively, afforded a substantial degree of protection against Haemonchus contortus to sheep. In vitro cultivation of the parasite usually yields a limited amount of these proteins and therefore, recom...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(97)00093-5
更新日期：1997-09-01 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：:Peptidomimetic inhibitors of mammalian zinc metalloproteases have been tested as potential agents for intervention in disease caused by kinetoplastid protozoa. Certain metalloprotease inhibitors were able to inhibit the release of variant surface glycoprotein from cultured transgenic procyclic Trypanosoma brucei, conf...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(01)00244-4
更新日期：2001-04-25 00:00:00
abstract：:The nucleotide sequence of two non-contiguous DNA fragments of 4.0 and 2.2 kb, respectively, of the kinetoplast maxicircle of Trypanosoma brucei brucei EATRO strain 427 has been determined, completing the sequence analysis of the so-called variable region (see also de Vries et al., 1988, Mol. Biochem. Parasitol. 27, 7...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(92)90178-m
更新日期：1992-12-01 00:00:00
abstract：:Schistosoma mansoni p14 gene encodes an eggshell precursor that is expressed only in vitelline cells of mature female worms in response to a male stimulus. The upstream region of the p14 gene contains several potential cis-acting regulatory sequences. We used the upstream region of the p14 gene as bait in a yeast-one-...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(00)00292-9
更新日期：2000-10-01 00:00:00
abstract：:The identification and characterization of a recombinant cDNA clone, designated OV9M, expressing an antigen present in Onchocerca volvulus infective larvae and adult stages is described. Clone OV9M was identified by screening a lambda gt11 cDNA expression library derived from adult O. volvulus mRNA using pooled rabbit...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(94)90122-8
更新日期：1994-05-01 00:00:00
abstract：:AF3 (AVPGVLRFamide) is an endogenous RFamide-like peptide isolated from the parasitic nematode Ascaris suum. It has a potent and long lasting excitatory effect in A. suum and Ascaridia galli. This is mediated by a mechanism independent of the nicotinic-like acetylcholine (ACh) receptor, which mediates excitatory trans...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(98)00039-5
更新日期：1998-06-01 00:00:00
abstract：:Three days after mice were inoculated with Trypanosoma brucei gambiense, total hepatic cytochrome P-450 levels were decreased 14% from control values, while the specific mixed-function oxidase activity (per nmole of cytochrome P-450) was inhibited almost 40% in infected animals. Furthermore, drugs used to treat trypan...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(81)90051-7
更新日期：1981-08-01 00:00:00
abstract：:Helicases are ubiquitous essential enzymes which have significant role in the nucleic acid metabolism. Using in silico approaches in the recent past we have identified a number of helicases in the Plasmodium falciparum genome. In the present study we report purification and detailed characterization of a novel helicas...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2010.12.003
更新日期：2011-03-01 00:00:00
abstract：:Contrary to previous reports in the literature, bloodstream forms of the haemoflagellate protozoan Trypanosoma brucei brucei are not deficient in their ability to metabolize hydrogen peroxide, although they either lack or only possess the normal enzymes for H2O2 detoxification, catalase (EC 1.11.1.6) and glutathione p...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(86)90023-x
更新日期：1986-08-01 00:00:00
abstract：:The removal of N-linked oligosaccharides by peptide-N4-[N-acetyl-beta-glucoseaminyl]asparagine amidase (previously known as aspartoglycosylamine amidohydrolase and abbreviated N-glycanase) from the surface of blood or insect-transmissible forms of Trypanosoma cruzi markedly increased the capacity of these organisms to...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(87)90040-5
更新日期：1987-01-15 00:00:00
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：:Entamoeba histolytica genomic organization and putative promoter elements appear to be distinct from both metazoan and better characterized protozoan organisms. The recent development of DNA-mediated transfection for E. histolytica enabled characterization of cis-acting promoter elements required for gene expression. ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(96)02614-x
更新日期：1996-06-01 00:00:00
abstract：:Erythrocytes from Plasmodium berghei-infected mice on incubation either in plasma or artificial isotonic media showed an increase in uptake of 45Ca2+ compared with erythrocytes from uninfected mice. Infected cells (55% parasitaemia) incubated in plasma from normal or infected mice gave uptake rates of 9.8 and 8.1 nmol...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(83)90023-3
更新日期：1983-03-01 00:00:00
abstract：:The merozoite of Plasmodium vivax possesses a high molecular mass surface protein called Pv-merozoite surface protein 1, PvMSP-1, which exhibits antigenic diversity among isolates. In this study, the extent of sequence variation in the polymorphic region and the flanking interspecies conserved blocks (ICBs) 5 and 6 of...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(96)02786-7
更新日期：1997-01-01 00:00:00
abstract：:Procyclic Trypanosoma brucei brucei strain 366D is susceptible to DL-alpha-difluoromethylornithine (DFMO) with an in vitro ED50 value of 225 microM. A mutant of the procyclic strain resistant to 20 mM of DFMO was isolated by serial in vitro passages of the organisms in increasing concentrations of the drug. Drug resis...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(87)90064-8
更新日期：1987-01-02 00:00:00
abstract：:Repeated DNA sequences have been instrumental in the development of DNA probes for many different parasites. Isolation of such DNA probes has generally been accomplished by differential screening of genomic libraries with total genomic DNA preparations. In the current work, a rational design strategy is presented for ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(93)90047-2
更新日期：1993-04-01 00:00:00
abstract：:The genus Cryptosporidium includes several species of intestinal protozoan parasites which multiply in intestinal epithelial cells. The impact of this infection on the transcriptome of cultured host cells was investigated using DNA microarray hybridizations. The expression of 14 genes found to be consistently up- or d...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2009.07.004
更新日期：2009-11-01 00:00:00
abstract：:The primary S(1) subsite specificity of a recombinant cysteine proteinase, CPB2.8 Delta CTE, of Leishmania mexicana was investigated in a systematic way using a series of peptides derived from Abz-KLRFSKQ-EDDnp in which Arg was substituted by all natural amino acids (where Abz is ortho-amino-benzoyl and EDDnp is N-[2,...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(01)00290-0
更新日期：2001-08-01 00:00:00
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 r...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2010.05.020
更新日期：2010-10-01 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
