Abstract:
:The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Taldone T,Gillan V,Sun W,Rodina A,Patel P,Maitland K,O'Neill K,Chiosis G,Devaney Edoi
10.1371/journal.pntd.0000714subject
Has Abstractpub_date
2010-06-15 00:00:00pages
e714issue
6eissn
1935-2727issn
1935-2735journal_volume
4pub_type
杂志文章abstract::Parasites of the Leishmania genus can rapidly alter several macrophage (MØ) signalling pathways in order to tame down the innate immune response and inflammation, therefore favouring their survival and propagation within their mammalian host. Having recently reported that Leishmania and bacterial LPS generate a signif...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000305
更新日期:2008-01-01 00:00:00
abstract::The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protect...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001645
更新日期:2012-01-01 00:00:00
abstract::Parasitic infections are a major source of human suffering, mortality, and economic loss, but drug development for these diseases has been stymied by the significant expense involved in bringing a drug though clinical trials and to market. Identification of single compounds active against multiple parasitic pathogens ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008150
更新日期:2020-03-20 00:00:00
abstract:BACKGROUND:Chagas disease is endemic to the southern Andean region of Ecuador, an area with one of the highest poverty rates in the country. However, few studies have looked into the epidemiology, vectors and transmission risks in this region. In this study we describe the triatomine household infestation in Loja provi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004142
更新日期:2015-10-06 00:00:00
abstract:BACKGROUND:Trachoma programs rely on guidelines made in large part using expert opinion of what will happen with and without intervention. Large community-randomized trials offer an opportunity to actually compare forecasting methods in a masked fashion. METHODS:The Program for the Rapid Elimination of Trachoma trials...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004000
更新日期:2015-08-24 00:00:00
abstract:BACKGROUND:In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities. METHOD...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003050
更新日期:2014-07-31 00:00:00
abstract::The mosquito Aedes aegypti, the principal vector of dengue virus, has recently been infected experimentally with Wolbachia: intracellular bacteria that possess potential as dengue biological control agents. Wolbachia depend on their hosts for nutrients they are unable to synthesize themselves. Consequently, competitio...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004320
更新日期:2016-01-08 00:00:00
abstract::The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a g...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002279
更新日期:2013-06-13 00:00:00
abstract::The niche conservatism hypothesis states that related species diverge in niche characteristics at lower rates than expected, given their lineage divergence. Here we analyze whether niche conservatism is a common pattern among vector species (Hemiptera: Reduviidae: Triatominae) of Trypanosoma cruzi that inhabit North a...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003266
更新日期:2014-10-30 00:00:00
abstract:BACKGROUND:Sensitization to Anisakis spp. can produce allergic reactions after eating raw or undercooked parasitized fish. Specific IgE is detected long after the onset of symptoms, but the changes in specific IgE levels over a long follow-up period are unknown; furthermore, the influence of Anisakis spp. allergen expo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004864
更新日期:2016-07-22 00:00:00
abstract:BACKGROUND:Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0004879
更新日期:2016-07-28 00:00:00
abstract::Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our unde...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008898
更新日期:2020-12-15 00:00:00
abstract::ELISA-based methods of detecting Fasciola cathepsins in feces are powerful techniques for diagnosing infections by F. hepatica and F. gigantica. In the last decade, the in-house MM3-COPRO ELISA and its commercial version BIO K 201 (BIO X Diagnostics, Belgium) have been recognized as useful tools for detecting early in...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004872
更新日期:2016-07-20 00:00:00
abstract::Sand flies are the insects responsible for transmitting Leishmania parasites, the causative agents of leishmaniasis in humans. However, the effects of sand fly breeding sites on their biology and ecology remain poorly understood. Herein, we studied how larval nutrition associated with putative breeding sites of the sa...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0009034
更新日期:2021-01-21 00:00:00
abstract::Dengue fever, a mosquito-borne viral disease in humans, has been endemic in many Southeast Asian countries. Since its first outbreak in 1978 in Foshan, Guangdong province, China, dengue has been continually epidemic in recent years in Guangdong, which raised the concern whether dengue infection is endemic in Guangdong...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008049
更新日期:2020-03-03 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pntd.0004223.]. ...
journal_title:PLoS neglected tropical diseases
pub_type: 已发布勘误
doi:10.1371/journal.pntd.0004394
更新日期:2016-01-13 00:00:00
abstract:BACKGROUND:Tick feeding causes extreme morbidity and mortality to humans through transmission of pathogens and causes severe economic losses to the agricultural industry by reducing livestock yield. Salivary gland secretions are essential for tick feeding and thus, reducing or preventing saliva secretions into the vert...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007153
更新日期:2019-02-07 00:00:00
abstract::Schistosomiasis is an important neglected tropical disease caused by digenean helminth parasites of the genus Schistosoma. Schistosomes are unusual in that they are dioecious and the adult worms live in the blood system. MicroRNAs play crucial roles during gene regulation and are likely to be important in sex differen...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002402
更新日期:2013-09-12 00:00:00
abstract::Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean....
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003055
更新日期:2014-08-07 00:00:00
abstract:BACKGROUND:Cutaneous leishmaniasis (CL) is a major public health concern in Turkey and Sanliurfa represents the most endemic city in Turkey. Although children are most commonly affected by CL, detailed studies of pediatric CL in Turkey are lacking. METHODOLOGY/PRINCIPAL FINDINGS:In this report we retrospectively evalu...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004835
更新日期:2016-07-14 00:00:00
abstract:OBJECTIVE:In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection and trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both the active trachoma sign "trachomatous inflammation-follicular" (TF) and ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005863
更新日期:2017-09-12 00:00:00
abstract::Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of cu...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008771
更新日期:2020-11-02 00:00:00
abstract:BACKGROUND:The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms an...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004586
更新日期:2016-04-05 00:00:00
abstract:BACKGROUND:Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined. METHODOLOGY/PRINCIPAL FINDINGS:We conducted a monocentric retrospective study...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003232
更新日期:2014-10-09 00:00:00
abstract::The 2015-2017 epidemics of Zika virus (ZIKV) in the Americas caused widespread infection, followed by protective immunity. The timing and burden of the next Zika virus outbreak remains unclear. We used an agent-based model to simulate the dynamics of age-specific immunity to ZIKV, and predict the future age-specific r...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007978
更新日期:2019-12-26 00:00:00
abstract:BACKGROUND:The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried ou...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001897
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005648
更新日期:2017-07-10 00:00:00
abstract::Rabies is a zoonotic infectious disease of the central nervous system (CNS). In unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. Despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004746
更新日期:2016-06-23 00:00:00
abstract:BACKGROUND:Taenia solium cysticercosis/taeniosis is emerging as a serious public health and economic problem in many developing countries. This study was conducted to determine prevalence and risk factors of human T. solium infections in Mbeya Region, Tanzania. METHODS AND FINDINGS:A cross-sectional survey was conduct...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002102
更新日期:2013-01-01 00:00:00
abstract::As rabies in carnivores is increasingly controlled throughout much of the Americas, bats are emerging as a significant source of rabies virus infection of humans and domestic animals. Knowledge of the bat species that maintain rabies is a crucial first step in reducing this public health problem. In North America, sev...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005541
更新日期:2017-05-19 00:00:00