Abstract:
BACKGROUND:Visceral leishmaniasis (VL) is hypoendemic in the Mediterranean region, where it is caused by the protozoan Leishmania infantum. An effective vaccine for humans is not yet available and the severe side-effects of the drugs in clinical use, linked to the parenteral administration route of most of them, are significant concerns of the current leishmanicidal medicines. New drugs are desperately needed to treat VL and phenotype-based High Throughput Screenings (HTS) appear to be suitable to achieve this goal in the coming years. METHODOLOGY/PRINCIPAL FINDINGS:We generated two infrared fluorescent L. infantum strains, which stably overexpress the IFP 1.4 and iRFP reporter genes and performed comparative studies of their biophotonic properties at both promastigote and amastigote stages. To improve the fluorescence emission of the selected reporter in intracellular amastigotes, we engineered distinct constructs by introducing regulatory sequences of differentially-expressed genes (A2, AMASTIN and HSP70 II). The final strain that carries the iRFP gene under the control of the L. infantum HSP70 II downstream region (DSR), was employed to perform a phenotypic screening of a collection of small molecules by using ex vivo splenocytes from infrared-infected BALB/c mice. In order to further investigate the usefulness of this infrared strain, we monitored an in vivo infection by imaging BALB/c mice in a time-course study of 20 weeks. CONCLUSIONS/SIGNIFICANCE:The near-infrared fluorescent L. infantum strain represents an important step forward in bioimaging research of VL, providing a robust model of phenotypic screening suitable for HTS of small molecule collections in the mammalian parasite stage. Additionally, HSP70 II+L. infantum strain permitted for the first time to monitor an in vivo infection of VL. This finding accelerates the possibility of testing new drugs in preclinical in vivo studies, thus supporting the urgent and challenging drug discovery program against this parasitic disease.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Calvo-Álvarez E,Stamatakis K,Punzón C,Álvarez-Velilla R,Tejería A,Escudero-Martínez JM,Pérez-Pertejo Y,Fresno M,Balaña-Fouce R,Reguera RMdoi
10.1371/journal.pntd.0003666subject
Has Abstractpub_date
2015-03-31 00:00:00pages
e0003666issue
3eissn
1935-2727issn
1935-2735pii
PNTD-D-14-02070journal_volume
9pub_type
杂志文章abstract:INTRODUCTION:While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different lif...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000326
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Increased vascular permeability is a hallmark feature in severe dengue virus (DV) infection, and dysfunction of endothelial cells has been speculated to contribute in the pathogenesis of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Rho-family GTPase Rac1 is a significant element of endothelial b...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000809
更新日期:2010-08-31 00:00:00
abstract::Mycetoma, one of the badly neglected tropical diseases, it is a localised chronic granulomatous inflammatory disease characterised by painless subcutaneous mass and formation of multiple sinuses that produce purulent discharge and grains. If untreated early and appropriately, it usually spread to affect the deep struc...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006391
更新日期:2018-05-10 00:00:00
abstract::Benzimidazole anthelmintics have long been employed for the control of soil-transmitted helminth infections. Flubendazole (FBZ) was approved in 1980 for the treatment of gastrointestinal nematode infections in both veterinary and human medicine. It has also long been known that parenteral administration of FBZ can lea...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0006436
更新日期:2019-01-16 00:00:00
abstract:BACKGROUND:There is a pressing need for drug discovery against visceral leishmaniasis, a life-threatening protozoal infection, as the available chemotherapy is antiquated and not bereft of side effects. Plants as alternate drug resources has rewarded mankind in the past and aimed in this direction, we investigated the ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007227
更新日期:2019-05-09 00:00:00
abstract::All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006280
更新日期:2018-02-23 00:00:00
abstract::We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004304
更新日期:2016-01-06 00:00:00
abstract:BACKGROUND:Visceral leishmaniasis (VL) is highly prevalent in the Indian state of Bihar and, without proper diagnosis and treatment, is associated with high fatality. However, lack of efficient reporting mechanism had been an impediment in estimating the burden of mortality and its antecedents among symptomatic VL case...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005150
更新日期:2016-11-21 00:00:00
abstract:BACKGROUND:A better understanding of reproductive processes in parasitic nematodes may lead to development of new anthelmintics and control strategies for combating disabling and disfiguring neglected tropical diseases such as lymphatic filariasis and onchocerciasis. Transcriptomatic analysis has provided important new...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000947
更新日期:2011-01-25 00:00:00
abstract:BACKGROUND:Burkholderia pseudomallei, a Tier 1 Select Agent and the cause of melioidosis, is a Gram-negative bacillus present in the environment in many tropical countries. Defining the global pattern of B. pseudomallei distribution underpins efforts to prevent infection, and is dependent upon robust environmental samp...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0002105
更新日期:2013-01-01 00:00:00
abstract::An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimat...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004824
更新日期:2016-07-14 00:00:00
abstract::This study focused on Oeosophagostomum sp., and more especially on O. bifurcum, as a parasite that can be lethal to humans and is widespread among humans and monkeys in endemic regions, but has not yet been documented in apes. Its epidemiology and the role played by non-human primates in its transmission are still poo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000630
更新日期:2010-03-16 00:00:00
abstract::The burden of leptospirosis in humans and animals in Africa is higher than that reported from other parts of the world. However, the disease is not routinely diagnosed in the continent. One of major factors limiting diagnosis is the poor availability of live isolates of locally circulating Leptospira serovars for incl...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004251
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that m...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002664
更新日期:2014-01-30 00:00:00
abstract:BACKGROUND:Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness. Here, we investigate whether protracted clearance of a primary infection in nonhuman primates is attributable to antigenic variation or related to the maturation of the anti-chlamydial humoral immune...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002248
更新日期:2013-05-30 00:00:00
abstract::Sporotrichosis is endemic in the Sub-Himalayan belt, which ranges from the northern to the north-eastern Indian subcontinent. Similar to many parts of the developing world, sporotrichosis is commonly recognized clinically in this region however consolidated epidemiological data is lacking. We report epidemiological, c...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001673
更新日期:2012-01-01 00:00:00
abstract::Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretro...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005634
更新日期:2017-05-25 00:00:00
abstract:BACKGROUND:Global deworming programs aim to reach 75% of at-risk preschool-age children (pre-SAC) by 2020. The 2013 global pre-SAC deworming coverage initially published by the World Health Organization (WHO) was 23.9%, but this estimate inadequately captured deworming delivered through Child Health Day (CHD) platforms...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004206
更新日期:2015-11-06 00:00:00
abstract::Animal African Trypanosomosis (AAT) presents a severe problem for agricultural development in sub-Saharan Africa. It is caused by several trypanosome species and current means of diagnosis are expensive and impractical for field use. Our aim was to discover antigens for the detection of antibodies to Trypanosoma congo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002936
更新日期:2014-06-12 00:00:00
abstract:BACKGROUND:Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1371/journal.pntd.0001273
更新日期:2011-11-01 00:00:00
abstract::Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished co...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007363
更新日期:2019-06-17 00:00:00
abstract::Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a va...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005586
更新日期:2017-05-22 00:00:00
abstract:BACKGROUND:Burkholderia pseudomallei is a soil saprophytic bacterium that causes melioidosis. The infection occurs through cutaneous inoculation, inhalation or ingestion. Bacteriophages (phages) in the same ecosystem may significantly impact the biology of this bacterium in the environment, and in their culturability i...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005005
更新日期:2016-09-26 00:00:00
abstract:BACKGROUND:Leptospirosis occurs worldwide, but the global incidence of human disease and its mortality are not well understood. Many patients are undiagnosed and untreated due to its non-specific symptoms and a lack of access to diagnostics. This study systematically reviews the literature to clarify the mortality from...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0003866
更新日期:2015-06-25 00:00:00
abstract:BACKGROUND:Trachoma is a major cause of blindness in Southern Sudan. Its distribution has only been partially established and many communities in need of intervention have therefore not been identified or targeted. The present study aimed to develop a tool to improve targeting of survey and control activities. METHODS...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000799
更新日期:2010-08-17 00:00:00
abstract::Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently ci...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005249
更新日期:2017-03-16 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::Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manif...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0002283
更新日期:2013-10-24 00:00:00
abstract:BACKGROUND:Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the saf...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001688
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Close to 800 million people in the world are at risk of schistosomiasis, 85 per cent of whom live in Africa. Recent studies have indicated that female genital schistosomiasis might increase the risk of human immunodeficiency virus (HIV) infection. The aim of this study is to quantify and analyse the characte...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001170
更新日期:2011-06-01 00:00:00