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role of camp signaling in the survival and infectivity of the protozoan parasite, leishmania donovani.leishmania donovani, while invading macrophages, encounters striking shift in temperature and ph (from 22°c and ph 7.2 to 37°c and ph 5.5), which act as the key environmental trigger for differentiation, and increases camp level and camp-mediated responses. for comprehensive understanding of camp signaling, we studied the enzymes related to camp metabolism. a stage-specific and developmentally regulated isoform of receptor adenylate cyclase (ldraca) showed to regulate differentiation-coupled ind ...201122091412
protective therapy with novel chromone derivative against leishmania donovani infection induces th1 response in vivo.background: visceral leishmaniasis is a chronic protozoan disease caused by leishmania donovani, an obligatory intracellular parasite that resides and multiplies within macrophages of the reticuloendothelial system. the aim of this study was to evaluate the efficacy of nine novel synthetic chromone derivatives as antileishmanial molecules in experimental murine visceral leishmaniasis. methods: in vitro activity of the molecules (2, 5 and 10 μg/ml) was assessed against promastigotes of both penta ...201122024637
phenology and population dynamics of sand flies in a new focus of visceral leishmaniasis in eastern azarbaijan province, north western of iran.to investigate species composition, density, accumulated degree-day and diversity of sand flies during april to october 2010 in azarshahr district, a new focus of visceral leishmaniasis in north western iran.201121914536
cryptolepine-induced cell death of leishmania donovani promastigotes is augmented by inhibition of autophagy.leishmania donovani are the causative agents of visceral leishmaniasis worldwide. lack of vaccines and emergence of drug resistance warrants the need for improved drug therapy and newer therapeutic intervention strategies against leishmaniasis. in the present study, we have investigated the effect of the natural indoloquinoline alkaloid cryptolepine on l. donovani ag83 promastigotes. our results show that cryptolepine induces cellular dysfunction in l. donovani promastigotes, which leads to the ...201122091398
antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model.2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. as this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. therefore, a 2-n-propylquinoline formulation, as cam ...201122091464
whole genome sequencing of multiple leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance.visceral leishmaniasis is a potentially fatal disease endemic to large parts of asia and africa, primarily caused by the protozoan parasite leishmania donovani. here, we report a high-quality reference genome sequence for a strain of l. donovani from nepal, and use this sequence to study variation in a set of 16 related clinical lines, isolated from visceral leishmaniasis patients from the same region, which also differ in their response to in vitro drug susceptibility. we show that whole-genome ...201122038251
detection of leishmania donovani infection using magnetic beads-based serum peptide profiling by maldi-tof ms in mice model.leishmaniasis is an important parasitic disease, and definite diagnosis using a specific and sensitive method is the first step to cure the disease. here, we present a novel diagnostic strategy based on serum peptide profiling by magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms). the serum peptides from the leishmani donovani-infected and healthy mice were enriched by the optimized magnetic beads. the mass spectrograms were acquired by ...201121850454
Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant Leishmania donovani.Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis (VL) and is responsible for significant mortality and morbidity. Increasing resistance towards antimonial drugs poses a great challenge in chemotherapy of VL. Paromomycin is an aminoglycosidic antibiotic and is one of the drugs currently being used in the chemotherapy of cutaneous and visceral leishmaniasis. To understand the mode of action of this antibiotic at the molecular level, we have investigated the global pro ...201122046323
Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani.Background & objectives: The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds. Methods: The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote a ...201122199112
expression of a leishmaniadonovani nucleotide sugar transporter in leishmaniamajor enhances survival in visceral organs.leishmania donovani and leishmaniainfantum infections cause fatal visceral leishmaniasis, and leishmaniamajor causes self healing cutaneous lesions. it is poorly understood what genetic differences between these leishmania species are responsible for the different pathologies of infection. to investigate whether l.donovani species-specific genes are involved in visceral leishmania infection, we have examined a l.donovani species-specific gene ld1590 (ortholog of linj15_v3.0900) that is a pseudog ...201121978449
cloning, expression, characterization, and inhibition studies on trypanothione synthetase, a drug target enzyme, from leishmania donovani.abstract trypanothione synthetase, a validated drug target, synthesizes trypanothione form glutathione (gsh) and spermidine. we report cloning, expressing, characterization and inhibition studies of trypanothione synthetase from leishmania donovani (ldtrys). the purified recombinant ldtrys enzyme obeyed michaelis-menten kinetics. high substrate inhibition was observed with glutathione (k(m)= 33.24 µm, k(cat)= 1.3s(-1), k(i)= 866 µm). enzyme obeyed simple hyperbolic kinetics with fixed glutathi ...201121972939
[A woman with a persisting ulcer on the chin].A 62-year-old woman presented with an ulcerative lesion on the chin. She had not visited tropical regions, but she had been in Cyprus. A skin biopsy revealed coccoid micro-organisms resembling Leishmania. Subsequently a PCR was performed which showed Leishmania donovani and Leishmania infantum complex and the diagnose 'cutaneous leishmaniasis' was confirmed.201122129807
IMP dehydrogenase deficiency in Leishmania donovani causes a restrictive growth phenotype in promastigotes but is not essential for infection in mice.Leishmania cannot synthesize purines de novo and therefore must scavenge purines from its host for survival and growth. Biochemical and genomic analyses have indicated that Leishmania species express three potential routes for the synthesis of guanylate nucleotides: (1) a two-step pathway that converts IMP to GMP; (2) a three-step pathway that starts with the deamination of guanine to xanthine, followed by phosphoribosylation to XMP and then conversion to GMP; or (3) direct guanine phosphoribosy ...201121907738
anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection.the present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-ccp), rheumatoid factor (rf), and circulating immune complexes (cic) in sudanese patients infected with the leishmania donovani parasite.201122124592
treatment of leishmania donovani-infected hamsters with miltefosine: analysis of cytokine mrna expression by real-time pcr, lymphoproliferation, nitrite production and antibody responses.miltefosine, an orally effective antileishmanial drug, works directly on the parasite by impairing membrane synthesis and subsequent apoptosis of the parasite and has also been reported to have macrophage-activating functions that aid parasite killing. we investigated the type of immunological responses generated in miltefosine-treated leishmania donovani-infected hamsters, which simulate the clinical situation of human kala-azar.201122121191
Morphometric and meristic characterization of Phlebotomus argentipes species complex in northern Sri Lanka: evidence for the presence of potential leishmaniasis vectors in the country.The transmission of cutaneous leishmaniasis (CL) is of public health concern in Sri Lanka. The parasite Leishmania donovani is reported to be the causative agent for CL in Sri Lanka. However there is no report on the vector of CL in the country. Phlebotomus argentipes sensu lato is the well known vector of L. donovani which causes visceral leishmaniasis (VL) in the nearby South India. The taxon Ph. argentipes previously reported to occur as a species complex comprising of two morphospe ...201122041744
visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the indian subcontinent? 201121980542
bioinformatic analysis of leishmania donovani long-chain fatty acid-coa ligase as a novel drug target.fatty acyl-coa synthetase (fatty acid: coa ligase, amp-forming; (ec 6.2.1.3)) catalyzes the formation of fatty acyl-coa by a two-step process that proceeds through the hydrolysis of pyrophosphate. fatty acyl-coa represents bioactive compounds that are involved in protein transport, enzyme activation, protein acylation, cell signaling, and transcriptional control in addition to serving as substrates for beta oxidation and phospholipid biosynthesis. fatty acyl-coa synthetase occupies a pivotal rol ...201122091399
Mechanism of Amphotericin B Resistance in Clinical Isolates of Leishmania donovani.The clinical value of Amphotericin B, the mainstay therapy for Visceral Leishmaniasis in Sodium Antimony Gluconate nonresponsive zones of Bihar, is now threatened by the emergence of acquired drug resistance and a comprehensive understanding of the underlying mechanisms is the need of the hour. We have selected an Amphotericin B resistant clinical isolate which demonstrated 8 fold higher LD(50) compared to sensitive strain to explore the mechanism of Amphotericin B resistance. Fluoremetric analy ...201122123699
Characterisation of antimony-resistant Leishmania donovani isolates: Biochemical and biophysical studies and interaction with host cells.Recent clinical isolates of Leishmania donovani from the hyperendemic zone of Bihar were characterised in vitro in terms of their sensitivity towards sodium stibogluconate in a macrophage culture system. The resulting half maximal effective concentration (EC(50)) values were compared with those of known sensitive isolates. Fifteen of the isolates showed decreased sensitivity towards SSG with an average EC(50) of 25.7±4.5µg/ml pentavalent antimony (defined as antimony resistant), whereas nine sho ...201121920365
Use of antimony in the treatment of leishmaniasis: current status and future directions.In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of ...201122091408
[Leishmania donovani: structural insignt in the recognition of C-methylated analogues of spermidine as natural polyamine].The ability of alpha-, beta-, gamma- and omega-methylated spermidine analogues to restore the growth of L. donovani promastigotes that were depleted of putrescine and spermidine was investigated. Only beta-methylated spermidine, like natural spermidine was capable of restoring the growth of L. donovani, while the remaining three analogues turned out to be inactive. Considering that alpha-methylated spermidine is a functionally active spermidine surrogate both in vivo and in vitro, this analogue ...201121954600
comparative assessment of a dna and protein leishmania donovani gamma glutamyl cysteine synthetase vaccine to cross-protect against murine cutaneous leishmaniasis caused by l. major or l. mexicana infection.leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. a vaccine which could cross-protect people against different leishmania spp. would facilitate control of this disease as more than one species of leishmania may be present. in this study the ability of a dna vaccine, using the full gene sequence for l. donovani gamma glutamyl cysteine synthetase (γgcs) incorporated in the pvax vector (pvaxγgcs), and a protein vaccine, using the correspondin ...201122210224
validation of a β-me elisa for detection of anti leishmania donovani antibodies in eastern sudan.a β-mercaptoethnol (β-me)-treated promastigote antigen of l. donovani was successfully employed in direct agglutination test (dat) for the diagnosis of visceral leishmaniasis (vl).201121931201
first report on ambisome-associated allergic reaction in two sudanese leishmaniasis patients.post kala-azar dermal leishmaniasis (pkdl) and mucosal leishmaniasis (ml) are serious clinical forms of leishmaniasis caused by leishmania donovani parasites in sudan. although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent pkdl and ml patients are treated with liposomal amphotericin b (ambisome) as a second-line drug. in this work, we report the development of allergic reactions by a pkdl and a ml sudanese patient to ambisome. th ...201121976565
molecular and serological detection of leishmania spp. in captive wild animals from ilha solteira, sp, brazil.leishmaniasis is a zoonotic disease that affects 12 million people worldwide. several mammalian species can serve as a reservoir for this disease. dogs are the main reservoir for visceral leishmaniasis in urban areas, which has become a serious public health concern in brazil. the aim of this study was to evaluate the presence of leishmania spp. in captive wild animals from ilha solteira, são paulo, brazil. blood and various tissues samples were collected from animals of five different species: ...201121961752
peripheral blood buffy coat smear: a promising tool for diagnosis of visceral leishmaniasis.confirmative diagnosis of visceral leishmaniasis (vl) is still being a challenge at the primary health care facilities in most of the rural endemic areas in the indian sub-continent. conventional methods for parasitological confirmation are risky and require skilled personnel hence, unreachable to the poor people in the endemic region. buffy coat smear microscopy, as a minimally invasive simple alternative, for the parasitological diagnosis of vl was evaluated in this prospective study. one hund ...201122205790
Leishman-Donovan bodies in the bone marrow biopsy. 201121866587
Genetic heterogeneity in clinical isolates of Leishmania donovani from India.Genetic diversity within 45 Indian Leishmania donovani isolates was analyzed using seven genetic markers. While kinetoplast DNA (kDNA) analysis revealed 15 genotypes, 8 genotypes were obtained by analysis of other markers. In contrast to earlier reports, our data suggest that significant genetic polymorphisms exist in L. donovani strains in Bihar, India. Our results confirm the presence of 2 zymodemes in India.201121865422
serum chemokine profiles in visceral leishmaniasis, hiv and hiv/ visceral leishmaniasis co-infected ethiopian patients.the search for a correlation between chemokine levels in plasma or serum and protection from hiv infection or progression to aids has been attempted by a number of workers. chemokines are also suggested to play a role in immunity to leishmania and leishmania co-infection with hiv.201121991751
Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial.Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial.201121931871
intracellular drug delivery in leishmania-infected macrophages: evaluation of saponin-loaded plga nanoparticles.drug delivery systems present an opportunity to potentiate the therapeutic effect of antileishmanial drugs. colloidal carriers are rapidly cleared by the phagocytic cells of the reticuloendothelial system (res), rendering them ideal vehicles for passive targeting of antileishmanials. this paper describes the development of poly(d,l-lactide-co-glycolide) (plga) nanoparticles (nps) for the antileishmanial saponin β-aescin. nps were prepared using the combined emulsification solvent evaporation/sal ...201122080813
Metabolic Variation during Development in Culture of Leishmania donovani Promastigotes.The genome sequencing of several Leishmania species has provided immense amounts of data and allowed the prediction of the metabolic pathways potentially operating. Subsequent genetic and proteomic studies have identified stage-specific proteins and putative virulence factors but many aspects of the metabolic adaptations of Leishmania remain to be elucidated. In this study, we have used an untargeted metabolomics approach to analyze changes in the metabolite profile as promastigotes of L. donova ...201122206037
Evasion of Host Defence by Leishmania donovani: Subversion of Signaling Pathways.Protozoan parasites of the genus Leishmania are responsible for causing a variety of human diseases known as leishmaniasis, which range from self-healing skin lesions to severe infection of visceral organs that are often fatal if left untreated. Leishmania donovani (L. donovani), the causative agent of visceral leishmaniasis, exemplifys a devious organism that has developed the ability to invade and replicate within host macrophage. In fact, the parasite has evolved strategies to interfere with ...201122091401
Paratransgenic control of vector borne diseases.Conventional methodologies to control vector borne diseases with chemical pesticides are often associated with environmental toxicity, adverse effects on human health and the emergence of insect resistance. In the paratransgenic strategy, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases th ...201122110385
Elongation Factor-2, a Th1 Stimulatory Protein of Leishmania donovani, Generates Strong IFN-? and IL-12 Response in Cured Leishmania-Infected Patients/Hamsters and Protects Hamsters against Leishmania Challenge.In visceral leishmaniasis, Th1 types of immune responses correlate with recovery from and resistance to disease, and resolution of infection results in lifelong immunity against the disease. Leishmanial Ags that elicit proliferative and cytokine responses in PBMCs from cured/exposed/Leishmania patients have been characterized through proteomic approaches, and elongation factor-2 is identified as one of the potent immunostimulatory proteins. In this study, we report the cloning and expression of ...201122079980
characterization of leishmania donovani aquaporins shows presence of subcellular aquaporins similar to tonoplast intrinsic proteins of plants.leishmania donovani, a protozoan parasite, resides in the macrophages of the mammalian host. the aquaporin family of proteins form important components of the parasite-host interface. the parasite-host interface could be a potential target for chemotherapy. analysis of l. major and l. infantum genomes showed the presence of five aquaporins (aqps) annotated as aqp9 (230aa), aqp putative (294aa), aqp-like protein (279aa), aqp1 (314aa) and aqp-like protein (596aa). we report here the structural mod ...201121969862
critical roles for light and its receptors in generating t cell-mediated immunity during leishmania donovani infection.light (tnfsf14) is a member of the tnf superfamily involved in inflammation and defence against infection. light signals via two cell-bound receptors; herpes virus entry mediator (hvem) and lymphotoxin-beta receptor (ltβr). we found that light is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (vl) caused by infection with the protozoan parasite leishmania donovani. light-hvem signalling is essential for early dendritic cell il-12/il-23p40 production, and the ...201121998581
Changing trends in visceral leishmaniasis: 10 years' experience at a referral hospital in Nepal.Visceral leishmaniasis (VL) is mainly confined to the southeast area in the Terai region of Nepal. This study aimed to assess time trends and geographical distribution of VL at a referral hospital over a 10-year period in Kathmandu, Nepal. A total of 1521 patients were admitted to the hospital during the study period (April 1999 to March 2009). Overall, 88% of cases were from endemic areas and 10% were from non-endemic areas. There was a significant decreasing trend in the number of VL cases in ...201121889181
synthesis and in vitro antiprotozoal activities of 5-phenyliminobenzo[a]phenoxazine derivatives.a series of 5-phenyliminobenzo[a]phenoxazine derivatives were synthesized. the in vitro antiprotozoal activities were evaluated against plasmodium falciparum k1, trypanosoma cruzi, leishmania donovani and trypanosoma brucei rhodesiense. n,n-diethyl-5-((4-methoxyphenyl)imino)-5h-benzo[a]phenoxazin-9-amine shows ic(50)=0.040 μmol l(-1) with a selective index of 1425 against plasmodium falciparum k1.201121868222
in vitro antiprotozoal activity of extracts of five turkish lamiaceae species.the in vitro antiprotozoal activities of crude methanolic extracts from the aerial parts of five lamiaceae plants (salvia tomentosa, s. sclarea, s. dichroantha, nepeta nuda subsp. nuda and marrubium astracanicum subsp. macrodon) were evaluated against four parasitic protozoa, i.e. trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and plasmodium falciparum. the cytotoxic potentials of the extracts on l6 cells were also evaluated. melarsoprol, benznidazole, miltefosine, chloroquine and ...201122224291
antiparasitic and antimicrobial isoflavanquinones from abrus schimperi.the etoh extract of abrus schimperi (fabaceae), collected in kenya, demonstrated significant activity against leishmania donovani promastigotes with ic50 value of 3.6 microg/ml. bioassay-guided fractionation of chcl3 fraction using centrifugal preparative tlc afforded two antiparasitic isoflavanquinones, namely amorphaquinone (1) and pendulone (2). they displayed ic50 values of 0.63 microg/ml and 0.43 microg/ml, respectively, against l. donovani promastigotes. both the compounds were also evalua ...201122224279
antimicrobial and antiprotozoal activities of secondary metabolites from the fungus eurotium repens.in this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1-8) isolated from the fungus eurotium repens. all compounds showed mild to moderate antibacterial or antifungal or both activities except 7. the activity of compound 6 was the best of the group tested. the in vitro antimalarial evaluation of these compounds revealed that compounds 1-3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and ...201123024574
characterization of the recent clinical isolates of indian kala-azar patients by rapd-pcr method.leishmaniasis is one of the most important vector borne diseases caused by kinetoplastid protozoa leishmania sp. among all forms of leishmaniasis, visceral leishmaniasis (vl) or kala-azar is the severest form of the illness. vl is characterized by fever, hepatosplenomegaly, anaemia, edema, weight loss and invariably fatal if left untreated. characterization of leishmania sp. is extremely necessary to understand the epidemiology, taxonomy and population genetics of the parasites which ultimately ...201123024491
synthesis and antikinetoplastid activity of a series of n,n'-substituted diamines.a series of 25 n,n'-substituted diamines were prepared by controlled reductive amination of free aliphatic diamines with different substituted benzaldehydes. the library was screened in vitro for antiparasitic activity on the causative agents of human african trypanosomiasis, chagas' disease and visceral leishmaniasis. the most potent compounds were derived from a subset of diamines that contained a 4-obn substitution, having a 50% parasite growth inhibition in the submicromolar (against trypano ...201122248858
role of remote sensing, geographical information system (gis) and bioinformatics in kala-azar epidemiology.visceral leishmaniasis or kala-azar is a potent parasitic infection causing death of thousands of people each year. medicinal compounds currently available for the treatment of kala-azar have serious side effects and decreased efficacy owing to the emergence of resistant strains. the type of immune reaction is also to be considered in patients infected with leishmania donovani (l. donovani). for complete eradication of this disease, a high level modern research is currently being applied both at ...201123554714
kala-azar in a brazilian child.we report the case of a six-year-old brazilian girl referred for splenomegaly who first presented with fever, asthenia, and weight loss. geographical location, clinical exam, and blood laboratories suggested kala-azar. serology confirmed kala-azar diagnosis, but direct evidence of the parasites was not made. a treatment by meglumine antimoniate is given under hospital surveillance for two weeks. thereupon, the patient is asymptomatic and all tests are normal.201124765289
kinetoplast morphology and segregation pattern as a marker for cell cycle progression in leishmania donovani.trypanosomatids are typified by uniquely configured mitochondrial dna--the kinetoplast. the replication timing of kinetoplast dna (kdna) is closely linked to nuclear s phase, but nuclear and kinetoplast compartments display staggered timing of segregation, post-replication. kinetoplast division is completed before nuclear division in trypanosoma species while nuclear division is completed first in crithidia species. leishmania donovani is the causative agent of visceral leishmaniasis, a form of ...201121401783
identification and characterization of a novel, 37-kilodalton leishmania donovani antigen for diagnosis of indian visceral leishmaniasis.the biggest challenge in the serological diagnosis of visceral leishmaniasis (vl) is to find a biomarker with a high specificity. this study was undertaken to identify novel leishmania donovani antigens to solve the existing problem. the soluble l. donovani promastigote antigen was separated by sds-page, and a western blot was probed with pooled sera of five subjects with confirmed vl before (n = 9 pools) and after (n = 9 pools) treatment and at the 6-month follow-up visit (n = 9 pools), healthy ...201121411602
in vitro screening of traditional south african malaria remedies against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum.three hundred extracts were prepared from plants traditionally used in south africa to treat malaria and screened in vitro for activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/ml, the ic (50) values against all four protozoal parasites and cytotoxic ic (50)s against rat myoblast l6 cells were determined. amongst the most notable re ...201121412695
expression of il-10-triggered stat3-dependent il-4ra is required for induction of arginase 1 in visceral leishmaniasis.although enhanced macrophage-specific arginase activity is directly related to increased parasite burden in cutaneous leishmaniasis (cl), the regulation and precise role of arginase in the disease outcome of visceral leishmaniasis (vl) has yet to be explored. as in cl, balb/c mice infected with leishmania donovani showed increased levels of arginase in acute infection. arginase 1 is the major isoform associated with infection and while the il-4-induced arginase pathway is operative in cl, il-10 ...201121413004
a clinical trial to evaluate the safety and immunogenicity of the leish-f1+mpl-se vaccine for use in the prevention of visceral leishmaniasis.healthy indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with leishmania donovani based on the direct agglutination test (dat). three cohorts of 6 dat-negative and 6 dat-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the leish-f1+mpl-se vaccine (consisting of 5µg, 10µg, or 20µg recombinant leishmania polyprotein leish-f1 antigen+25µg mpl®-se adjuv ...201121414377
therapy with sodium stibogluconate in stearylamine-bearing liposomes confers cure against ssg-resistant leishmania donovani in balb/c mice.resistance of leishmania donovani to pentavalent antimonials, the first-line treatment of visceral leishmaniasis (vl), has become a critical issue worldwide. second-line and new drugs are also not devoid of limitations. suitable drug-delivery systems can improve the mode of administration and action of the existing antimonials, thus increasing their clinical life.201121423750
leishmania donovani glycosphingolipid facilitates antigen presentation by inducing relocation of cd1d into lipid rafts in infected macrophages.nkt cells respond to presentation of specific glycolipids with release of both th1- and th2-type cytokines. leishmania donovani (ld)-infected splenic macrophages (sm?(i)) and bone marrow-derived dendritic cells (bmdc(i)) failed to activate nkt cells in response to a-galactosyl ceramide (a-galcer). the defective antigen presentation could be corrected by treating the cells with the immunostimulating glycosphingophospholipid (gspl) of ld parasites. in vitro pulsing of bmdc(i) or sm?(i) with gspl, ...201121425159
novel compounds to combat trypanosomatid infections: a medicinal chemical perspective.introduction: the current therapeutic arsenal against the kinetoplastids trypanosoma brucei, trypanosoma cruzi and leishmania spp. is clearly inadequate and underscores the urgent need to develop new effective, safe and cost-effective drugs. areas covered: accordingly, this review of patented products and processes using anti-kinetoplastid agents provides insight into the identification of novel or more refined drugs. in this review, we describe products developed in recent years for the treatme ...201121428846
anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of +¦-bromo-6h-1,3,4-oxadiazine derivatives.cyanoacetylhydrazine reacted with the ¤ë-bromoacetophenones 2a,b to give hydrazide-hydrazone derivatives 3a,b. the latter products were cyclized to the 1,3,4-oxadiazine derivatives 4a,b. bromination of the latter products gave the 6-bromo-6h-1,3,4-oxadiazine derivatives 5a,b which underwent a series of cross-coupling reactions. the antitumor evaluation of the newly synthesized products against the three cancer cells namely breast adenocarcinoma (mcf-7), non-small cell lung cancer (nci-h460) and ...201121435889
the use of conjunctival swab samples for pcr screening for visceral leishmaniasis in vaccinated dogs.the polymerase chain reaction (pcr) has been shown to provide a rapid and sensitive technique for leishmania detection. the aim of this study was to evaluate the technique of noninvasive conjunctival swabs (cs) as a sampling method for molecular screening for visceral leishmaniasis (vl) in a group of 42 police dogs, all of them vaccinated against vl, and to compare the results with those obtained by serological tests. the serological assays were performed independently by three laboratories. lab ...201121439230
a novel a2 allele found in leishmania (leishmania) infantum chagasi.visceral leishmaniasis (vl) is a widely spread zoonotic disease. in brazil the disease is caused by leishmania (leishmania)infantum chagasi. peridomestic sandflies acquire the etiological agent by feeding on blood of infected reservoir animals, such as dogs or wildlife. the disease is endemic in brazil and epidemic foci have been reported in densely populated cities all over the country. many clinical features of leishmania infection are related to the host-parasite relationship, and many candid ...201121439231
leishmania aflp: paving the way towards improved molecular assays and markers of diversity.diversity, phylogenetic, and population genetic studies of the genus leishmania, causative agent of leishmaniasis, nowadays generally involve multilocus microsatellite and multilocus sequence typing. even though these are well established and useful applications, amplified fragment length polymorphisms (aflp) can provide complementary information. in addition, as the technique essentially probes the entire genome at random, without prior sequence knowledge, it is ideally suited as a screening to ...201121439405
a high-throughput turbidometric assay for screening inhibitors of leishmania major protein disulfide isomerase.the use of a high-throughput technique to perform a pilot screen for leishmania major protein disulfide isomerase (lmpdi) inhibitors identification is reported. in eukaryotic cells, protein disulfide isomerase (pdi) plays a crucial role in protein folding by catalyzing the rearrangement of disulfide bonds in substrate proteins following their synthesis. lmpdi displays similar domain structure organization and functional properties to other pdi family members and is involved in leishmania virulen ...201121441416
effect of a2 gene on infectivity of the nonpathogenic parasite leishmania tarentolae.several species of protozoan parasites of the genus leishmania are pathogenic to mammals and cause a wide spectrum of pathologies in human. however, the genus includes some species which infect reptiles. leishmania tarentolae is a lizard pathogen absolutely nonpathogenic to mammals. recent studies have shown that among some major virulence factors, a2 is absent in this species. first identified as an amastigote-specific gene in leishmania donovani, a2 has been proved to play a major role in para ...201121442256
adaptation of a 2d in-gel kinase assay to trace phosphotransferase activities in the human pathogen leishmania donovani.the protozoan parasite leishmania donovani undergoes various developmental transitions during its infectious cycle that are triggered by environmental signals encountered inside insect and vertebrate hosts. intracellular differentiation of the pathogenic amastigote stage is induced by ph and temperature shifts that affect protein kinase activities and downstream protein phosphorylation. identification of parasite proteins with phosphotransferase activity during intracellular infection may reveal ...201121443974
biophysical and folding parameters of trypanothione reductase from leishmania infantum.out of various tropical diseases caused by trypanosomatids, leishmaniasis is a life-threatening disease caused by the leishmania parasite. we are targeting the thiol metabolic pathway of the parasite for drug development, and trypanothione reductase (tryr) is a key enzyme of this pathway. it is important to gather significant knowledge about biophysical and intrinsic properties of this enzyme which will be helpful in better understanding of this drug-target enzyme. we report here the modulation ...201121445596
structure-activity relationship investigations of leishmanicidal n-benzylcytisine derivatives.in vitro leishmanicidal activity of 16 n-benzylcytisine derivatives has been evaluated using leishmania donovani axenic amastigotes. in general, halogen (bromo-, chloro-) derivatives appeared to be more toxic against parasites than their parent compounds. quantum-chemical calculations helped to recognize certain patterns in the structure of frontier orbitals related to bioactivity of compounds. thus, the presence of halogen atom is shown to have a significant effect on both distribution and the ...201121457471
leishmania express a functional cdc20 homologue.our knowledge concerning the mechanisms of cell cycle regulation in organisms belonging to the trypanosometidae family is limited. leishmania donovani are parasitic protozoa that cause kala azar, a fatal form of visceral leishmaniasis in humans. here we provide evidence that the l. donovani genome contains a cdc20 homologue. cdc20 is a regulator of the anaphase promoting complex/cyclosome (apc/c) that mediates ubiquitin-dependent proteasomal degradation of key cell cycle regulators in eukaryotes ...201121458414
cutaneous leishmaniasis after travel to cyprus and successful treatment with miltefosine.a patient presenting with an atypical manifestation of cutaneous leishmaniasis after travel to cyprus was successfully treated with miltefosine. the k26 typing revealed a hitherto undescribed strain of the leishmania donovani/infantum complex as the causing agent.201121460010
antimony-resistant clinical isolates of leishmania donovani are susceptible to paromomycin and sitamaquine.widespread antimonial resistance in anthroponotic visceral leishmaniasis (vl) makes it critical to monitor the susceptibility of prevailing field isolates to upcoming antileishmanials in order to frame the right treatment policies to protect these drugs against development of resistance. we aimed to generate the baseline data on natural in vitro susceptibility to paromomycin and sitamaquine in leishmania donovani field isolates from vl patients (n = 20) coming from zones of varying sodium antimo ...201121464251
berberine chloride mediates its anti-leishmanial activity via differential regulation of the mitogen activated protein kinase pathway in macrophages.a complex interplay between leishmania and macrophages influences parasite survival and necessitates disruption of signaling molecules, eventually resulting in impairment of macrophage function. in this study, we demonstrate the immunomodulatory activity of berberine chloride in leishmania infected macrophages.201121483684
recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature.the characteristics of 8 episodes of leishmaniasis with atypical manifestations in 2 italian kidney transplant recipients are analyzed and contextualized among those of 52 other episodes of leishmaniasis observed in 19 transplant recipients found through a systematic review of the international literature. in all the patients, the initial episode was visceral leishmaniasis, which was associated with mucocutaneous involvement in 2 cases. with the exception of 1 case of post kala-azar dermal leish ...201121281418
antileishmania immunological tests for asymptomatic subjects living in a visceral leishmaniasis-endemic area in brazil.the objective of this study was to evaluate the behavior of different tests used for the diagnosis of visceral leishmaniasis (vl) in asymptomatic subjects living in an endemic area. no gold standard is available for the diagnosis of asymptomatic infection with leishmania. in continuation of a previous study, 1,017 subjects living in a vl-endemic area were clinically reevaluated. of these, 576 had at least one positive serological test in a first assessment. about 3 years after the first evaluati ...201121292896
design and synthesis of novel tetrahydronaphthyl azoles and related cyclohexyl azoles as antileishmanial agents.a novel series of trans-2-aryloxy-1,2,3,4,-tetrahydronaphthyl azoles and related cyclohexyl azoles were synthesized and evaluated in vitro against leishmania donovani. compound 9 identified as most active analog with ic(50) value of 0.64 µg/ml and si value of 34.78 against amastigotes, and is several folds more potent than the reference drugs sodium stilbogluconate and paromomycin. it also exhibited significant in vivo inhibition of 83.33%, and provided a new structural scaffold for antileishman ...201121295472
cell cycle arrest evidence, parasiticidal and bactericidal properties induced by l-amino acid oxidase from bothrops atrox snake venom.the present article describes an l-amino acid oxidase from bothrops atrox snake venom as with antiprotozoal activities in trypanosoma cruzi and in different species of leishmania (leishmania braziliensis, leishmania donovani and leishmania major). leishmanicidal effects were inhibited by catalase, suggesting that they are mediated by h(2)o(2) production. leishmania spp. cause a spectrum of diseases, ranging from self-healing ulcers to disseminated and often fatal infections, depending on the spe ...201121300133
role of unique basic residues in cytotoxic, antibacterial and antiparasitic activities of human eosinophil cationic protein.eosinophil granule proteins, eosinophil cationic protein (ecp) and eosinophil-derived neurotoxin are members of the rnase a superfamily, which play a crucial role in host defense against various pathogens as they are endowed with several biological activities. some of the biological activities possessed by ecp have been attributed to its strong basic character. in the current study, we have investigated the role of five unique basic residues, arg22, arg34, arg61, arg77 and his64 of ecp in its ca ...201121303303
potency, efficacy and durability of dna/dna, dna/protein and protein/protein based vaccination using gp63 against leishmania donovani in balb/c mice.visceral leishmaniasis (vl) caused by an intracellular protozoan parasite leishmania, is fatal in the absence of treatment. at present there are no effective vaccines against any form of leishmaniasis. here, we evaluate the potency, efficacy and durability of dna/dna, dna-prime/protein-boost, and protein/protein based vaccination against vl in a susceptible murine model.201121311597
ubiquitination of mrna cycling sequence binding protein from leishmania donovani (ldcsbp) modulates the rna endonuclease activity of its smr domain.in trypanosomatid parasites, an octanucleotide sequence (c/a)auagaa(g/a) in the utrs primarily determines the stability of s-phase specific mrnas. a multi-domain protein ldcsbp from leishmania donovani interacts with the utr of an s-phase rna containing the octanucleotide sequence through its unique ccch-type zn-finger motifs. interestingly, the rna binding protein contains a previously characterized dna endonuclease domain - smr. it has been demonstrated here that the ldcsbp smr domain independ ...201121315716
visceral leishmaniasis: experimental models for drug discovery.visceral leishmaniasis (vl) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. the causative agent is a haemoflagellate protozoan leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. as an alternate strategy, vaccination is also under exper ...201121321417
reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in leishmania amazonensis.leishmaniasis, a parasitic disease caused by protozoa of the genus leishmania, affects more than 12 million people worldwide. quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. one such activity is exhibited against the bloodstream parasite trypanosoma brucei and amastigotes of leishmania donovani. however, the mechanism of protozoan action of quercetin has not been studied.201121346801
didemnidines a and b, indole spermidine alkaloids from the new zealand ascidian didemnum sp.two new indole spermidine alkaloids, didemnidines a (1) and b (2), have been isolated from the new zealand ascidian didemnum sp. the structures of the metabolites, determined by analysis of 2d nmr spectra and confirmed via synthesis, embody an indole-3-glyoxylamide moiety linked to the n(1) position of spermidine, the latter motif being particularly rare among marine natural products. didemnidine b and a synthetic precursor exhibited mild in vitro growth inhibition of plasmodium falciparum with ...201121348447
bioinformatic analysis of glycogen synthase kinase 3: human versus parasite kinases.summaryobjective. glycogen synthase kinase 3 (gsk-3) is a promising target for the treatment of various human diseases such as type 2 diabetes, alzheimer's disease and inflammation. successful inhibition of the homologues of this kinase in plasmodium falciparum, trypanosoma brucei and leishmania donovani makes the kinase an attractive target for the treatment of malaria, trypanosomiasis and leishmaniasis, respectively. the aim of this work was to compare the binding sites of the gsk-3 kinases of ...201121349219
generating knock-in parasites: integration of an ornithine decarboxylase transgene into its chromosomal locus in leishmania donovani.leishmania null mutants created by targeted gene replacement are typically complemented with chimeric episomes harboring the replaced gene in order to validate that the observed phenotype is due to the specific gene deletion. however, the current inventory of available episomes for complementation of genetic lesions in leishmania is unstable in the absence of drug selection, and levels of gene expression cannot be controlled, especially in vivo. to circumvent this impediment, a strategy to re-in ...201121354142
identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system.new drugs are needed to treat visceral leishmaniasis (vl) because the current therapies are toxic, expensive, and parasite resistance may weaken drug efficacy. we established a novel ex vivo splenic explant culture system from hamsters infected with luciferase-transfected leishmania donovani to screen chemical compounds for anti-leishmanial activity.201121358812
in vitro refolding of triosephosphate isomerase from l. donovani.the triosephosphate isomerase of leishmania donovani (ldtim) was expressed at high level in escherichia coli. the tim gene was cloned in expression vector pet-23(a) with c-terminal 6× his tag fused in frame, and expressed as a 27.6-kda protein in e. coli as inclusion bodies. the recombinant ldtim from e. coli lysate was solubilized in 6 m guanidine hydrochloride and purified by ni-nta chromatography. in the present study, the effect of bovine serum albumin on the reactivation of tim was investig ...201121365180
ecology and control of the sand fly vectors of leishmania donovani in east africa, with special emphasis on phlebotomus orientalis.a literature review is provided on the state of knowledge of the ecology and control of the sand fly vectors of leishmania donovani in east africa, with a special emphasis on phlebotomus orientalis. visceral leishmaniasis caused by l. donovani is a major health problem in several areas in east africa. studies conducted in the past 70 years identified p. orientalis parrot and p. martini parrot as the principal vectors of l. donovani in sudan, ethiopia and kenya and p. celiae minter as the seconda ...201121366778
distribution and ecological aspects of sand fly (diptera: psychodidae) species in sri lanka.human indigenous cutaneous leishmaniasis caused by leishmania donovani complex is endemic in sri lanka. we performed an entomological survey to determine the distribution of probable vector species. sand flies were collected in districts in the dry zone, in the wet zone highlands, and in the wet zone coastal belt of sri lanka using cdc light traps, sticky traps and cattle-baited net traps during july, 2005. the survey was reconducted in february, 2006. overall, 584 sand flies belonging to phlebo ...201121366784
biochemical characterization of dipeptidylcarboxypeptidase of leishmania donovani.the incidence of parasitic infection, leishmaniasis, has been steadily increasing worldwide. since, the existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance, there is an urgent need for development of potent, mechanism-based anti-parasitic agents. the peptidases of protozoan parasites are becoming increasingly important for their role in parasite survival and pathogenecity. leishmania donovani dipeptidylcarboxypep ...201121366963
serological evidence of leishmania donovani infection in apparently healthy dogs using direct agglutination test (dat) and rk39 dipstick tests in kafta humera, north-west ethiopia.leishmania (kinetoplastida: trypanosomatidae) are protozoan parasites of significant medical and veterinary importance. over the last decade, visceral leishmaniasis (vl) has emerged as a major opportunistic infection associated with hiv/aids in north western ethiopia. this paper reports on serological evidence of possible leishmania donovani (l. donovani) infection in dogs using two serological tests: direct agglutination test (dat) and kalazar detect rapid test (kdrt). two hundred and seventeen ...201121371289
multilocus microsatellite typing revealed high genetic variability of leishmania donovani strains isolated during and after a kala-azar epidemic in libo kemkem district, northwest ethiopia.in 2004, an outbreak of kala-azar (ka) occurred for the first time in libo kemkem district, in the highland area of northwest ethiopia. in order to track the possible origins of the outbreak parasites, we have investigated 19 strains of leishmania donovani that were collected during (n = 6) and after (n = 13) the outbreak by using 14 highly polymorphic microsatellite markers. unique microsatellite profiles were obtained for all strains from libo kemkem. when compared to those of l. donovani stra ...201121382503
antiparasitic and antimicrobial indolizidines from the leaves of prosopis glandulosa var. glandulosa*a new indolizidine alkaloid, named +ö(1,6)-juliprosopine ( 1), together with previously known indolizidine analogs ( 2- 6), was isolated from the leaves of prosopis glandulosa var. glandulosa, collected from nevada, usa; while two other known indolizidines, juliprosopine ( 6) and juliprosine ( 7), were isolated from p. glandulosa leaves collected in texas, usa. the structures of compound 1 and 7 were determined using a combination of nmr and ms techniques. compound 7 exhibited potent antiplasmod ...201121384317
synthesis and evaluation of new furanyl and thiophenyl azoles as antileishmanial agents.a series of benzyloxy furanyl and benzyloxy thiophenyl azoles were synthesized and screened for their in vitro antileishmanial activity against leishmania donovani. among all, 16 compounds have shown more than 90% inhibition against promastigotes at 20 ++m while 11 compounds exhibited ic50 in the range of 3.04-9.39 ++m against amastigotes. compound 4, a 3-chlorobenzyloxy furanyl imidazole emerged as the most active compound in the series with ic50 value of 3.04 ++m and si value of 19.80, and was ...201121385661
noninvasive molecular diagnosis of human visceral leishmaniasis.previously developed methods for noninvasive pcr diagnosis of visceral leishmaniasis (vl) have significant limitations. diagnosis of vl using pcr and buccal swabs was evaluated in 307 subjects, including 148 patients confirmed to have vl. this method is simple and well tolerated and has good potential for development, showing 83% sensitivity with 90.56% specificity in control groups.201121389158
in vitro interactions between sitamaquine and amphotericin b, sodium stibogluconate, miltefosine, paromomycin and pentamidine against leishmania donovani.to evaluate in vitro interactions between sitamaquine and the current antileishmanial drugs amphotericin b, sodium stibogluconate, miltefosine, paromomycin and pentamidine against intracellular leishmania donovani amastigotes in peritoneal mouse macrophages. a second objective was to evaluate the susceptibility of antimony-resistant l. donovani isolates to sitamaquine.201121393188
targeted killing of leishmania donovani in vivo and in vitro with amphotericin b attached to functionalized carbon nanotubes.this study describes the antileishmanial efficacy of the novel drug formulation of amphotericin b (amb) attached to functionalized carbon nanotubes (f-cnts) and compares it with amb.201121393222
fucoidan cures infection with both antimony-susceptible and -resistant strains of leishmania donovani through th1 response and macrophage-derived oxidants.the aim of this study was to evaluate and characterize the antileishmanial efficacy of fucoidan, a polyanionic sulphated polysaccharide from brown algae, in experimental infections of balb/c mice with antimony-susceptible (ag83) and -resistant (ge18er) leishmania donovani.201121393231
in vitro activities of new 2-substituted quinolines against leishmania donovani.a series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. the 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (ic(50)) of 1.2 μm and a selectivity index value of 121.5. compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60 ...201121220526
combination therapy with paromomycin-associated stearylamine-bearing liposomes cures experimental visceral leishmaniasis through th1-biased immunomodulation.visceral leishmaniasis (vl) caused by the parasite leishmania donovani is a potentially fatal disease. available limited drugs are toxic, require prolonged treatment duration, and are costly. a low-cost parenteral formulation of paromomycin sulfate (pm) has recently been approved for the treatment of vl. monotherapy with pm runs the risk of development of resistance. hence, efforts are needed to develop a combination therapy of pm with other drugs to shorten the duration of treatment and prolong ...201121220536
species delimitation and phylogenetic relationships of chinese leishmania isolates reexamined using kinetoplast cytochrome oxidase ii gene sequences.leishmaniasis is a geographically widespread disease caused by protozoan parasites belonging to the genus leishmania and transmitted by certain species of sand fly. this disease still remains endemic in china, especially in the west and northwest frontier regions. a recent its1 phylogeny of chinese leishmania isolates has challenged some aspects for their traditional taxonomy and cladistic hypotheses of their phylogeny. however, disagreement with respect to relationships within chinese leishmani ...201121221640
cocktail of gp63 and hsp70 induces protection against leishmania donovani in balb/c mice.the 63-kda antigen of leishmania donovani is a membrane-anchored matrix metalloprotease that has been shown to be involved in the infection process. we have shown that this antigen alone generates a th1 type of protective response that is partial but when the animals are primed with the antigen along with the hsp70, the level of protection is raised significantly, which is demonstrated by a considerable reduction in parasite load of immunized animals when compared to the infected controls. delay ...201121226722
critical role of irf-5 in the development of t helper 1 responses to leishmania donovani infection.the transcription factor interferon regulatory factor 5 (irf-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and tlr activation and to play an essential role in the innate inflammatory response. in this study, we used the experimental model of visceral leishmaniasis to investigate the role of irf-5 in the generation of th1 responses and in the formation of th1-type liver granulomas in leishmania donovani infected mice. we show that t ...201121253574
molecular detection and genetic diversity of leishmania donovani in naturally infected phlebotomus chinensi from southwestern china.zoonotic visceral leishmaniasis is an important vector-borne infectious disease in western china. in this study, an epidemiological study was carried out on the vector of zoonotic visceral leishmaniasis in rural areas from sichuan province, southwestern china. in the 1263 phlebotomine sandflies captured, 859 (68.01%) were females and 404 (31.99%) males, belonging to phlebotomus chinensis (83.37%), sergentomyia koloshanensis (6.57%), sergentomyia squamirostris (4.04%), and sergentomyia barraudi ( ...201121254870
a new atp-binding cassette protein is involved in intracellular haem trafficking in leishmania.the characterization of labcg5, a new intracellular atp-binding cassette protein in leishmania donovani, is described. unlike other abcg half-transporters, labcg5 is not involved in either drug resistance or phospholipid efflux. however, we provide evidence suggesting that this protein is involved in intracellular haem trafficking. thus, downregulation of labcg5 function produced upon overexpression of an inactive version of the protein caused a dramatic growth arrest unless a haemin supplement ...201121255121
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