Abstract：
:Toxoplasma gondii is a protozoan parasite of great importance in human and veterinary health. The frontline treatment of antifolates suffers a variety of drawbacks, including toxicity and allergic reactions, underscoring the need to identify novel drug targets for new therapeutics to be developed. We previously showed that the Toxoplasma lysine acetyltransferase (KAT) GCN5b is an essential chromatin remodeling enzyme in the parasite linked to the regulation of gene expression. We have previously established that the KAT domain is a liability that can be targeted in the parasite by compounds like garcinol; here, we investigate the potential of the bromodomain as a targetable element of GCN5b. Bromodomains bind acetylated lysine residues on histones, which helps stabilize the KAT complex at gene promoters. Using an inducible dominant-negative strategy, we found that the GCN5b bromodomain is critical for Toxoplasma viability. We also found that the GCN5-family bromodomain inhibitor, L-Moses, interferes with the ability of the GCN5b bromodomain to associate with acetylated histone residues using an in vitro binding assay. Moreover, L-Moses displays potent activity against Toxoplasma tachyzoites in vitro, which can be overcome if parasites are engineered to over-express GCN5b. Collectively, our data support the GCN5b bromodomain as an attractive target for the development of new therapeutics.
journal_name
Exp Parasitoljournal_title
Experimental parasitologyauthors
Hanquier J,Gimeno T,Jeffers V,Sullivan WJ Jrdoi
10.1016/j.exppara.2020.107868subject
Has Abstractpub_date
2020-02-28 00:00:00pages
107868eissn
0014-4894issn
1090-2449pii
S0014-4894(19)30596-Xjournal_volume
211pub_type
杂志文章abstract：:This study presents the first genetic characterization of five Trypanosoma rangeli isolates from Minas Gerais, in the southeast of Brazil and their comparison with Colombian populations by minicircle classification, RAPD-PCR and LSSP-PCR analyses. Our results demonstrated a homogenous T. rangeli population circulating...
journal_title：Experimental parasitology
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doi：10.1016/j.exppara.2007.03.007
更新日期：2007-09-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2012.11.011
更新日期：2013-02-01 00:00:00
abstract：:The intestine of Haemonchus contortus is hypersensitive to the effects of the anthelmintic fenbendazole (FBZ). The effects are postulated to stem from disruption of microtubules and interference with apical secretory vesicle transport, followed by release of digestive enzymes into the intestinal cell cytoplasm. Here, ...
journal_title：Experimental parasitology
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doi：10.1016/s0014-4894(02)00135-2
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abstract：:M17 leucine aminopeptidase (LAP) is one of a family of metalloexopeptidases, of which short peptide fragments are cleaved from the N-terminals. In this study, the full length of cDNA encoding Fasciola gigantica LAP (FgLAP) was cloned from adult parasites. The amino acid sequences of FgLAP showed a high degree of ident...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2012.04.008
更新日期：2012-07-01 00:00:00
abstract：:High-throughput drug screening methods against the intracellular stage of Leishmania have been facilitated by the development of in vitro models of infection. The use of cell lines rather than primary cells facilitates these methods. Peripheral blood mononuclear cell (PBMC) derived macrophages and THP-1 cells were inf...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2010.06.007
更新日期：2010-12-01 00:00:00
abstract：:An NADP-linked glutamate dehydrogenase (EC 1.4.1.4) was found in the soluble fraction of Trichomonas vaginalis. Its molecular weight was about 230,000 (gel filtration). The enzyme, partially purified by diafiltration and hydroxyapatite column chromatography, was heat stable (1 hr at 57 C). It catalyzed both the aminat...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(88)90007-0
更新日期：1988-10-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(88)90124-5
更新日期：1988-04-01 00:00:00
abstract：:Chromosome-sized DNA molecules from Trypanosoma cruzi clone Dm 28c were analyzed and compared with other T. cruzi strains and monogenetic trypanosomatids by orthogonal field alteration gel electrophoresis. The results showed that T. cruzi Dm 28c displays at least 18 chromosomes ranging from 550 to more than 1500 kb an...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(89)90178-1
更新日期：1989-08-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1006/expr.1996.0018
更新日期：1996-03-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/s0014-4894(03)00032-8
更新日期：2002-10-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(85)90071-2
更新日期：1985-04-01 00:00:00
abstract：:Nitric oxide (NO), derived from catalysis of inducible NO synthase (iNOS), limits malaria parasite growth in mammals. Transforming growth factor (TGF)-beta1 suppresses iNOS in cells in vitro as well as in vivo in mice, but paradoxically severe malaria in humans is associated with low levels of TGF-beta1. We hypothesiz...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2007.08.013
更新日期：2008-02-01 00:00:00
abstract：:Schistosomiasis is one of the world's greatly neglected tropical diseases, and its control is largely dependent on a single drug, praziquantel. Here, we report the in vitro effect of piplartine, an amide isolated from Piper tuberculatum (Piperaceae), on Schistosoma mansoni adult worms. A piplartine concentration of 15...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2010.08.021
更新日期：2011-02-01 00:00:00
abstract：:Plasma butyrylcholinesterase (BChE) hydrolyzes ester-containing compounds such as succinylcholine, as well as acting as a scavenger against neurotoxic organophosphates (OPs). We previously found that Nippostrongylus brasiliensis infection makes rats more susceptible to OP toxicity by decreasing serum paraoxonase-1 (PO...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2009.02.009
更新日期：2009-06-01 00:00:00
abstract：AIM:The present study investigated the processes of macrogametogenesis and oocyst formation of Eimeria tenella (Xiamen strain), including the formation of wall-forming body1 (WFB1) and wall-forming body 2 (WFB2), the club-shape body and the origin of the residual body during the transformation from a macrogamete to an ...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2006.01.001
更新日期：2006-07-01 00:00:00
abstract：:The anthelmintic fenbendazole (FBZ) induces nuclear DNA fragmentation (DF) in intestinal cells of Haemonchus contortus. The DNA fragments had 3'-OH, which suggests involvement of a neutral DNase. To identify candidate DNase(s) involved, DNase activity in H. contortus intestine and other worm fractions was characterize...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/s0014-4894(03)00136-x
更新日期：2003-07-01 00:00:00
abstract：:The burden of Plasmodium vivax malaria is huge in India, affecting a large population annually. Recent reports of P. vivax contributing to severe illness and death, makes vaccine research on P. vivax malaria, a high priority. Extent of sequence variation in antigen coding genes is known to be a major hurdle in vaccine...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2013.02.004
更新日期：2013-05-01 00:00:00
abstract：:Advanced molecular biology techniques are currently used to develop new effective strategies against fasciolosis. Assessment of the quality of extracted total RNA is an important step prior to commencing many molecular biology methods such as transcriptomics. However, RNA quality assessment is complicated for some org...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2013.07.026
更新日期：2013-10-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1006/expr.1994.1091
更新日期：1994-11-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(86)90036-6
更新日期：1986-12-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/0014-4894(90)90026-9
更新日期：1990-08-01 00:00:00
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journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1006/expr.2000.4569
更新日期：2000-11-01 00:00:00
abstract：:Cystic echinococcosis (CE) is caused by the larval stage of Echinococcus granulosus, which in this disease the metacestode develop in visceral organs especially liver and lungs. The disease is present worldwide and affects humans as well as herbivores including cattle, sheep, camels, horses and others. Benzimidazole c...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2013.07.017
更新日期：2013-10-01 00:00:00
abstract：:This review focuses on the role of IL-4 in the immune response which develops during infection with the trematode parasite Schistosoma mansoni. The emphasis is on our own recent studies in the mouse model. ...
journal_title：Experimental parasitology
pub_type： 杂志文章,评审
doi：10.1006/expr.1996.0116
更新日期：1996-11-01 00:00:00
abstract：:Resistance of human pathogens like Leishmania to drugs is a growing concern where the multidrug-resistant phenotype renders chemotherapy ineffective. The acquired resistance of Leishmania to antimony has promoted intense research on the mechanisms involved but the question has not been resolved yet. In this study we h...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2017.02.019
更新日期：2017-05-01 00:00:00
abstract：:In this first report about pinworms peptidases we primarily characterize peptidases released during in vitro maintenance of two common pinworms of laboratory animals -Syphacia muris and Passalurus ambiguus. The peptidase activity obtained using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showe...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2010.04.018
更新日期：2010-10-01 00:00:00
abstract：:In this work, an ecto-phosphatase activity of Entamoeba histolytica was characterized using intact cells. This activity presented the following biochemical characteristics: (i) it hydrolyzes p-NPP with V(max) of 8.00+/-0.22 nmol p-NP x h(-1) x 10(-5) cells and K(m) of 2.68+/-0.25 mM; (ii) it is inhibited by acid phosp...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2006.09.019
更新日期：2007-04-01 00:00:00
abstract：:There is evidence which suggests that malaria sporozoites recognize mosquito salivary glands by specific receptor-ligand interactions. We are interested in identifying the putative salivary gland receptor(s) for sporozoite invasion. We used an in vivo bioassay for sporozoite invasion of salivary glands. In this assay,...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1006/expr.1995.1124
更新日期：1995-11-01 00:00:00
abstract：:Parasites of wildlife inhabiting urbanised and peri-urban environments are of interest regarding wildlife population health, and also veterinary public health in the case of parasites that can also infect humans and domestic animals. This study aimed to: identify, and estimate the prevalence of, species of Eimeria par...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2016.09.012
更新日期：2016-11-01 00:00:00
abstract：:This study aimed to evaluate the susceptibility of Brazilian isolates of Trypanosoma evansi to suramin sodium. For this purpose, three isolates of T. evansi (LPV-2005, LPV-2009 and LPV-2010) and seventy mice were used, with the animals divided in 10 groups (A, B, C, D, E, F, G, H, I and J) with seven animals each grou...
journal_title：Experimental parasitology
pub_type： 杂志文章
doi：10.1016/j.exppara.2013.03.027
更新日期：2013-07-01 00:00:00
