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differential role of leptin as an immunomodulator in controlling visceral leishmaniasis in normal and leptin-deficient mice.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani there are no vaccines and available drugs against leishmaniasis are toxic. immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. therefore, finding novel immunomodulators for vl therapy is a pressing need. this study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the imm ...201627114296
genomic appraisal of the multifactorial basis for in vitro acquisition of miltefosine resistance in leishmania donovani.protozoan parasites of the leishmania donovani complex are the causative agents of visceral leishmaniasis (vl), the most severe form of leishmaniasis, with high rates of mortality if left untreated. leishmania parasites are transmitted to humans through the bite of infected female sandflies (diptera: phlebotominae), and approximately 500,000 new cases of vl are reported each year. in the absence of a safe human vaccine, chemotherapy, along with vector control, is the sole tool with which to figh ...201627114280
alkanediamide-linked bisbenzamidines are promising antiparasitic agents.a series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two trypanosoma brucei (t.b.) subspecies: t.b. brucei and t.b. rhodesiense, trypanosoma cruzi, leishmania donovani and two plasmodium falciparum subspecies: a chloroquine-sensitive strain (nf54) and a chloroquine-resistant strain (k1). the in vitro cytotoxicity was determined against rat myoblast cells (l6). seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against bot ...201627104545
mechanistic insight into the reactivation of bcaii enzyme from denatured and molten globule states by eukaryotic ribosomes and domain v rrnas.in all life forms, decoding of messenger-rna into polypeptide chain is accomplished by the ribosome. several protein chaperones are known to bind at the exit of ribosomal tunnel to ensure proper folding of the nascent chain by inhibiting their premature folding in the densely crowded environment of the cell. however, accumulating evidence suggests that ribosome may play a chaperone role in protein folding events in vitro. ribosome-mediated folding of denatured proteins by prokaryotic ribosomes h ...201627099964
antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.a small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. all tested compounds were active or moderately active against trypanosoma cruzi amastigotes in infected l6 cells and trypanosoma brucei brucei, four of eleven compounds were moderately active against leishmania donovani axenic parasites while none were deemed active against t. brucei rhodesiense. for the mo ...201627092415
repeated training of accredited social health activists (ashas) for improved detection of visceral leishmaniasis cases in bihar, india.accredited social health activists (ashas) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (vl). one of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and d ...201627077313
correction: leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol. 201627073882
a role for adenine nucleotides in the sensing mechanism to purine starvation in leishmania donovani.purine salvage by leishmania is an obligatory nutritional process that impacts both cell viability and growth. previously, we have demonstrated that the removal of purines in culture provokes significant metabolic changes that enable leishmania to survive prolonged periods of purine starvation. in order to understand how leishmania sense and respond to changes in their purine environment, we have exploited several purine pathway mutants, some in which adenine and guanine nucleotide metabolism is ...201627062185
apoptotic protein profile in leishmania donovani after treatment with hexaazatrinaphthylenes derivatives.two hexaazatrinaphthylene derivatives, dgv-b and dgv-c previously known to induce an apoptotic-like process in leishmania donovani parasites were used in this study. for this purpose, two different human protein commercial arrays were used to determine the proteomic profile of the treated parasites compared to non-treated ones. one of the commercial arrays is able to detect the relative expression of 35 human apoptosis-related proteins and the other one is able to identify 9 different human kina ...201627060614
comparative analysis of cellular immune responses in treated leishmania patients and hamsters against recombinant th1 stimulatory proteins of leishmania donovani.our prior studies demonstrated that cellular response of t helper 1 (th1) type was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kda) of leishmania donovani promastigote, in treated leishmania patients as well as hamsters and showed significant prophylactic potential against experimental visceral leishmaniasis (vl). eighteen th1 stimulatory proteins were identified through proteomic analysis of this subfraction, out of which 15 were developed as recombinant proteins. in th ...201627047452
cd271+ mesenchymal stem cells as a possible infectious niche for leishmania infantum.visceral leishmaniasis (vl) is a serious and fatal disease. therapeutic drugs are toxic and non-sterilizing. the etiological agents leishmania infantum and leishmania donovani cause active and asymptomatic diseases. effective drugs to treat vl exist but unfortunately, post-treatment relapses are common. little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. here, using a murine model of vl we found that cd271+/sca1+ bone marrow mesenchymal stem c ...201627622907
transgenic t cell-specific expression of cxcr3 enhances splenic and hepatic t cell accumulation but does not affect the outcome of visceral leishmaniasis.the outcome of visceral leishmaniasis, caused by parasite leishmania donovani, depends on the recruitment of leishmanicidal th1 cells. chemokine receptor cxcr3, preferentially expressed by th1 cells, is critical for migration of these t cells during infection. during chronic vl, there is a decrease in the presence of cxcr3-expressing cd4(+) t cells in the spleen, which is associated with high parasitic burden in this organ. we therefore examined whether t cell-specific expression of cxcr3 in mic ...201627614845
molecular modeling and virtual screening approach to discover potential antileishmanial inhibitors against ornithine decarboxylase.visceral leishmaniasis (vl) is a tropical neglected disease, which encounters poorest of poor people living in asia, africa and latin america; causes the mortality of more than 30,000 people worldwide. the armamentarium for the treatment of vl cases is limited and continuously facing decreasing of efficacy for existing drugs. ornithine decarboxylase (odc) is one of the interesting drug targets in leishmania donovani, due to its association with redox metabolism.201627604958
antileishmanial mechanism of diamidines involves targeting kinetoplasts.leishmaniasis is a disease caused by pathogenic leishmania parasites; current treatments are toxic and expensive, and drug resistance has emerged. while pentamidine, a diamidine-type compound, is one of the treatments, its antileishmanial mechanism of action has not been investigated in depth. here we tested several diamidines, including pentamidine and its analog db75, against leishmania donovani and elucidated their antileishmanial mechanisms. we identified three promising new antileishmanial ...201627600039
antileishmanial ferrocenylquinoline derivatives: synthesis and biological evaluation against leishmania donovani.the emergence of resistance against existing antileishmanial drugs necessitates the search for new classes of antileishmanial compounds. herein a series of structurally diverse ferrocenylquinolines have been synthesized and evaluated for in vitro antileishmanial activity against leishmania donovani using the mtt assay. thirteen (m2-m14) substituted ferrocenylquinoline congeners possessing triazole rings were generated by palladium mediated suzuki-miyaura coupling reaction of 5-iodoferrocenylquin ...201627598235
magnesium-dependent ecto-atp diphosphohydrolase activity in leishmania donovani.in this work, we have described the expression of ecto-atpdase on the external surface of leishmania donovani. this enzyme has the ability to hydrolyze extracellular atp. there is a low level of atp hydrolysis in the absence of divalent cation 2.5 ± 0.51 nm pi 10(7) cells/h which shows the divalent cation-dependent activity of this enzyme in the intact parasite. however, mgcl2 stimulated the atp hydrolysis to a greater extent compared with cacl2 and zncl2. this activity was also observed when re ...201627589852
live attenuated leishmania donovani centrin knock out parasites generate non-inferior protective immune response in aged mice against visceral leishmaniasis.visceral leishmaniasis (vl) caused by the protozoan parasite leishmania donovani causes severe disease. age appears to be critical in determining the clinical outcome of vl and at present there is no effective vaccine available against vl for any age group. previously, we showed that genetically modified live attenuated l. donovani parasites (ldcen-/-) induced a strong protective innate and adaptive immune response in young mice. in this study we analyzed ldcen-/- parasite mediated modulation of ...201627580076
taxonomic and predicted metabolic profiles of the human gut microbiome in pre-columbian mummies.characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. we characterized the gut microbiome of two pre-columbian andean mummies dating to the 10-15th centuries using 16s rrna gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century ad pre-columbian andean mummy. our previous study sh ...201627559027
the immunology of post-kala-azar dermal leishmaniasis (pkdl).post-kala-azar dermal leishmaniasis (pkdl) is a common complication of visceral leishmaniasis (vl) caused by leishmania donovani. because of its possible role in transmission it is considered a public health problem in vl endemic areas. the clinical features include a skin rash consisting of macules, papules or nodules in an otherwise healthy individual; this presentation is determined by the immune response towards parasites in the skin that probably persisted from the previous vl episode. the ...201627553063
nitrotriazole-based acetamides and propanamides with broad spectrum antitrypanosomal activity.3-nitro-1h-1,2,4-triazole-based acetamides bearing a biphenyl- or a phenoxyphenyl moiety have shown remarkable antichagasic activity both in vitro and in an acute murine model, as well as substantial in vitro antileishmanial activity but lacked activity against human african trypanosomiasis. we have shown now that by inserting a methylene group in the linkage to obtain the corresponding propanamides, both antichagasic and in particular anti-human african trypanosomiasis potency was increased. th ...201627543881
immunogenicity and protective efficacy of dna vaccine against visceral leishmaniasis in balb/c mice.the current study was designed to examine the protective efficacy of dna vaccines based on gp63 and hsp70 against murine visceral leishmaniasis. inbred balb/c mice were immunized subcutaneously twice at an interval of three weeks with pcdna3.1(+) encoding t cell epitopes of gp63 and hsp70 individually and in combination. animals were challenged intracardially with 10(7) promastigotes of leishmania donovani 10 days post immunization and sacrificed 1, 2 and 3 months post challenge. the immunized a ...201627533939
pitfalls in the synthesis of fluorescent methotrexate oligopeptide conjugates.methotrexate (mtx) conjugates with poly[lys(dl-alam)] based polymeric polypeptides are efficient against leishmania donovani parasite infection, but the mechanism of the effect is not known yet. we prepared therefore the 5(6)-carboxyfluorescein (cf) labeled oligopeptide [cf-k(aaaa)] (a: d-alanine, a: l-alanine) and the corresponding mtx conjugates [cf-k(mtx-aaaa)] as model compounds for structure-activity experiments. the conjugate aimed to be synthesized with solid phase methodology on mbha res ...201627357306
visual assessment of parasitic burden in infected macrophage by plasmonic detection of leishmania specific marker rna.visceral leishmaniasis is a neglected tropical disease and may prove fatal if not diagnosed and treated early. the amastigotes of leishmania donovani nest in the macrophage of human host and thus, determination of parasitic burden in the infected macrophages has been the most crucial step in diagnosis, dose determination and medical management of relapse cases of this fatal disease. microscopic count following giemsa staining and other morphological analysis are the classical ways vastly used in ...201627720714
leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through akt-mediated regulation of β-catenin and foxo-1.in order to establish infection, intra-macrophage parasite leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. in the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator akt for modulating its downstream transcription factors, β-catenin and foxo-1. l. donovani-infected raw264.7 and bone marrow-derived macrophages (bmdm) treated with akt inhibitor or dominant negative akt constructs showe ...201627662364
noninvasive diagnosis of visceral leishmaniasis: development and evaluation of two urine-based immunoassays for detection of leishmania donovani infection in india.visceral leishmaniasis (vl), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. post kala-azar dermal leishmaniasis (pkdl), a skin related outcome, is a potential reservoir for the spread of vl. diagnostic tests available for vl such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. serological tests although less invasive than tissue aspiration are incompetent to assess cure. parasitological examination o ...201627741241
development of leishmania donovani stably expressing dsred for flow cytometry-based drug screening using chalcone thiazolyl-hydrazone as a new antileishmanial target.green fluorescent protein produces significant fluorescence and is extremely stable, however its excitation maximum is close to the ultraviolet range and thus can damage living cells. hence, leishmania donovani stably expressing dsred were developed and their suitability for flow cytometry-based antileishmanial screening was assessed by evaluating the efficacies of standard drugs as well as newly synthesised chalcone thiazolyl-hydrazone compounds. the dsred gene was successfully integrated at th ...201627876275
leishmania donovani-induced increase in macrophage bcl-2 favors parasite survival.members of the bcl-2 family are major regulators of apoptosis in mammalian cells, and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. in this investigation, we uncover a novel role of host bcl-2 in sustaining leishmania donovani infection. a rapid twofold increase in bcl-2 expression occurred in response to parasite challenge. downregulation of post infection bcl-2 increase using sirna or functiona ...201627826299
oleanolic acid loaded poly lactic co- glycolic acid- vitamin e tpgs nanoparticles for the treatment of leishmania donovani infected visceral leishmaniasis.oleanolic acid (oa) has low aqueous solubility and low permeability, which results poor bioavailability. to surmount the inadequacy, our aim was to fabricate oleanolic acid loaded poly lactic co- glycolic acid (plga)- d-α- tocopheryl polyethylene glycol 1000 succinate (tpgs) nanoparticles, which could be efficacious for the treatment of leishmania donovani mediated visceral leishmaniasis (vl). oa loaded plga- tpgs nanoparticles were prepared by emulsion solvent evaporation technique. cellular up ...201627645930
pharmacovigilance of miltefosine in treatment of visceral leishmaniasis in endemic areas of bihar, india.miltefosine, the only oral drug for visceral leishmaniasis (vl), is being used as the first-line drug under the vl elimination program in the indian subcontinent. miltefosine is an oral drug which was used as a topical application for skin metastasis of breast cancer. it was found to be effective against leishmania donovani the main adverse events (ae) reported previously with miltefosine use includes diarrhea, vomiting, and dehydration. other aes include, raised serum alanine transaminase/aspar ...201627645786
glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in leishmania donovani.various physiological stimuli trigger the conversion of noninfective leishmania donovani promastigotes to the infective form. here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. however, this was reversed by supplementation of gluconeogenic amino acids. glucose starvation induced metacyclogenesis and enhanced virulence through pro ...201627664030
ancistectorine d, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8'- and 7,1'-linked metabolites from the chinese liana ancistrocladus tectorius.from the twigs and stems of the chinese liana ancistrocladus tectorius (ancistrocladaceae), two new 5,8'-coupled naphthylisoquinolines, ancistectorine d (5) and its 6-o-demethyl derivative 6, were isolated, along with two new 7,1'-linked alkaloids, 6-o-methylancistectorine b1 (7) and ancistectorine b2 (8). two further compounds, ancistroealaine a (4) and 6-o-demethyl-8-o-methyl-7-epi-ancistrobrevine d (10), already known from related asian and african ancistrocladus species, were discovered for ...201627646602
genetic markers for antimony resistant clinical isolates differentiation from indian kala-azar.visceral leishmaniasis or kala-azar is caused by the protozoan parasites belonging to the genus leishmania. once thought eradicated from the indian subcontinent, the disease came back with drug resistance to almost all prevalent drugs. molecular epidemiological studies revealed the polymorphic nature of the population of the main player of the disease, leishmania donovani and involvement of other species (l. tropica) and other genus (leptomonas) with the disease. this makes control measures almo ...201627629023
dna sequencing confirms pcr-rflp identification of wild caught larroussius sand flies from crete and cyprus.many phlebotomine sand fly species (diptera, psychodidae) are vectors of the protozoan parasite leishmania causing a group of diseases called the leishmaniases. the subgenus larroussius includes sand fly vectors found in south east mediterranean basin responsible for visceral (vl) and cutaneous human leishmaniasis (cl). it is important to monitor these medically important insects in order to safely predict possible leishmania transmission cycles. leishmania infantum is endemic in the islands of ...201627609635
recombinant leishmania rab6 (rldrab6) is recognized by sera from visceral leishmaniasis patients.rab proteins form the largest branch of the ras superfamily. rab proteins are key regulators of intracellular vesicular transport and membrane trafficking. although rabgtpases are well-recognized targets in human diseases but are under-explored therapeutically in the leishmania parasite. using a quantitative cytofluorimetric assay, we analyzed the composition and organization of rab6gtpase protein which was found to be primarily localized on the parasite subpellicular membrane and flagellum due ...201627666959
phenotypic characterization of a leishmania donovani cyclophilin 40 null mutant.protozoan parasites of the genus leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. using a null mutant approach we previously revealed important, nonredundant functions of the cochaperone cyclophilin 40 in l. donovani-infected macrophages. here, we characterized in more detail the virulence defect of cyp40-/- null mu ...201627216143
safety and efficacy of a combination of paromomycin and miltefosine for two versus three courses in patients with post kala-azar dermal leishmaniasis (pkdl) - an observational pilot study.pkdl is a dermal form of leishmaniasis caused by protozoal parasite leishmania donovani. it is characterized by macular, popular and nodular lesions or a mixture of these(1) . it is mainly seen in sudan and india, where it follows treatment of visceral leishmaniasis (vl) in 50% and 5-10% of cases respectively(2) . a phase iii study on miltefosine-paromomycin combination for 10 days for treatment of indian visceral leishmaniasis (n=157) revealed high cure rate (98.7%) with minimal toxicity, good ...201627781268
immunotherapeutic potential of eugenol emulsion in experimental visceral leishmaniasis.the therapy of visceral leishmaniasis (vl) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in hiv-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (cmi). thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. several plant-derived compounds have been found to exert leishmanicidal act ...201627776125
protective inflammatory response against visceral leishmaniasis with potato tuber extract: a new approach of successful therapy.the increasing number of drug resistance issue of leishmania donovani strain to common drugs compels to develop new therapeutics against leishmaniasis with minimal toxicity. in this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. the important roles of leishmania proteases in the virulence of leishmania parasite make them very hopeful targets for the improvement of current remedial of leishmaniasis. as part of a hunt for new drugs, we hav ...201627567589
integrated machine learning, molecular docking and 3d-qsar based approach for identification of potential inhibitors of trypanosomal n-myristoyltransferase.n-myristoyltransferase (nmt) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. it is a studied and validated pre-clinical drug target for fungal and parasitic infections. in the present study, a machine learning approach, docking studies and comfa analysis have been integrated with the objective of translation o ...201627766319
identification of internalin-a-like virulent proteins in leishmania donovani.an active immune surveillance and a range of barriers to infection allow the host to effectively eliminate microbial pathogens. however, pathogens may use diverse strategies to subdue such host defences. for instance, one such mechanism is the use of leucine-rich repeat (lrr) proteins by pathogens (microbial) to cause infection. in this study, we aimed at identifying novel virulence factor(s) in leishmania donovani, based on the possibility of lateral gene transfers of bacterial virulence factor ...201627765050
loop-mediated isothermal amplification assay as a sensitive diagnostic tool for leishmania donovani infections in sri lanka.cutaneous leishmaniasis (cl) in sri lanka is caused by leishmania donovani mon 37. confirmation of diagnosis is done through microscopy, either directly or after in vitro culture. molecular diagnostic methods are sensitive, but require well established laboratories. loop mediated isothermal amplification assay (lamp) is rapid, specific for parasite speciesspecific dna amplification, and requires only basic laboratory equipment. the aim of the study was to determine the potential utility of lamp ...201627423747
ongoing outbreak of cutaneous leishmaniasis in northwestern yemen: clinicoepidemiologic, geographic, and taxonomic study.cutaneous leishmaniasis (cl) is widespread in yemen but has not been fully documented.201627419356
evaluation of s.c. route of immunization by homologous radio attenuated live vaccine in experimental murine model of visceral leishmaniasis.our previous studies in balb/c mice showed substantial protection against the experimental murine visceral leishmaniasis (mvl) when the animals were immunized with γ-irradiated live leishmania donovani parasites through intra peritoneal (i.p.) and intra muscular (i.m.) routes respectively. the observations encouraged us to check the prophylactic efficacy of subcutaneous (s.c.) route as it is better alternative for human trial. the mice immunized with two subsequent doses of the radio attenuated ...201627413317
molecular detection of infection homogeneity and impact of miltefosine treatment in a syrian golden hamster model of leishmania donovani and l. infantum visceral leishmaniasis.control of visceral leishmaniasis caused by leishmania infantum and leishmania donovani primarily relies on chemotherapy using an increasingly compromised repertoire of antileishmanial compounds. for evaluation of novel drugs, the syrian golden hamster is considered as a clinically relevant laboratory model. in this study, two molecular parasite detection assays were developed targeting cathepsin-like cysteine protease b (cpb) dna and 18s rrna to achieve absolute amastigote quantification in the ...201627412759
immunoprotective effect of lentinan in combination with miltefosine on leishmania-infected j-774a.1 macrophages.rejuvenation of deteriorated host immune functions is imperative for successful annihilation of leishmania parasites. the use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. we herein investigated the immunostimulatory potency of a β-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on leishmania-infected j-774a.1 macrophages. our study shows ...201627387601
molecular and serological evidence of leishmania infection in stray dogs from visceral leishmaniasis-endemic areas of bangladesh.visceral leishmaniasis (vl), or kala-azar, is mainly caused by two closely related leishmania species, leishmania infantum and leishmania donovani leishmania infantum is responsible for zoonotic vl, with dogs as the main reservoir host in the mediterranean, the middle east, asia, and south america. in the indian subcontinent, vl is caused by l. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. the role of domestic and stray dogs in vl ...201627382083
twin attributes of tyrosyl-trna synthetase of leishmania donovani: a housekeeping protein translation enzyme and a mimic of host chemokine.aminoacyl-trna synthetases (aarss) are housekeeping enzymes essential for protein synthesis. apart from their parent aminoacylation activity, several aarss perform non-canonical functions in diverse biological processes. the present study explores the twin attributes of leishmania tyrosyl-trna synthetase (ldtyrrs) namely, aminoacylation, and as a mimic of host cxc chemokine. leishmania donovani is a protozoan parasite. its genome encodes a single copy of tyrosyl-trna synthetase. we first tested ...201627382051
corrigendum: leishmanicidal activity of piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by th1 immunostimulatory potential in vivo.[this corrects the article on p. 1368 in vol. 6, pmid: 26696979.].201627379073
2.8-å cryo-em structure of the large ribosomal subunit from the eukaryotic parasite leishmania.leishmania is a single-cell eukaryotic parasite of the trypanosomatidae family, whose members cause an array of tropical diseases. the often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs, and emerging resistant strains, underline the need to develop strategies to combat these pathogens. the trypanosomatid ribosome has recently been highlighted as a promising therapeutic target due to structural features that are distinct from other eukaryotes. he ...201627373148
tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired ifn-γ production by spleen cells from human visceral leishmaniasis patients.the pro-inflammatory cytokine tumor necrosis factor (tnf)-α has an important role in control of experimental leishmania donovani infection. less is known about the role of tnf-α in human visceral leishmaniasis (vl). evidence for a protective role is primarily based on case reports of vl development in individuals treated with tnf-α neutralizing antibody. in this study, we have evaluated how tnf-α neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (sa ...201627372917
gmp reductase and genetic uncoupling of adenylate and guanylate metabolism in leishmania donovani parasites.purine acquisition is an essential nutritional process for leishmania. although purine salvage into adenylate nucleotides has been investigated in detail, little attention has been focused on the guanylate branch of the purine pathway. to characterize guanylate nucleotide metabolism in leishmania and create a cell culture model in which the pathways for adenylate and guanylate nucleotide synthesis can be genetically uncoupled for functional studies in intact cells, we created and characterized n ...201627343371
molecular detection, identification and phylogenetic inference of leishmania spp. in some desert lizards from northwest china by using internal transcribed spacer 1 (its1) sequences.leishmaniasis caused by leishmania is still endemic in northwest china. it has been thought that reptiles could be a reservoir for mammalian leishmaniasis. however, data are still scarce on natural infection of lizards with leishmania spp. in china. the present study deals with detection, identification and phylogenetic inference of leishmania parasites at species and intraspecies levels isolated from six desert lizard species from 10 geographical locations in northwest china using amplification ...201627338182
corrigendum: identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors. 201627323004
plumbagin, a plant-derived naphthoquinone metabolite induces mitochondria mediated apoptosis-like cell death in leishmania donovani: an ultrastructural and physiological study.naphthoquinones are known to exhibit a broad range of biological activities against microbes, cancer and parasitic diseases and have been widely used in indian traditional medicine. plumbagin is a plant-derived naphthoquinone metabolite (5-hydroxy-2-methyl-1,4-naphthoquinone) reported to inhibit trypanothione reductase, the principal enzyme and a validated drug target involved in detoxification of oxidative stress in leishmania. here, we report the mechanistic aspects of cell death induced by pl ...201627315817
activity of a novel sulfonamide compound 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide against leishmania donovani.new treatments for visceral leishmaniasis, caused by leishmania donovani, are needed to overcome sustained toxicity, cost, and drug resistance. the aim of this study was to evaluate the therapeutic effects of 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide (2nb) against promastigote and amastigote forms of l. donovani and examine its effect in combination with amphotericin b (amb) against amb-resistant clinical isolates. effects were assessed against extracellular promastigotes in vitro and int ...201627307706
association of hla class i and ii genes with cutaneous leishmaniasis: a case control study from sri lanka and a systematic review.the outcome of leishmaniasis is an interplay between leishamania and the host. identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. leishmaniasis is caused exclusively by l. donovani in sri lanka with localized cutaneous leishmaniasis (lcl) being the predominant form. we report here an association study of human leucocyte antigen (hla) class i and ii genes with lcl in sri lanka, the first on hla associations in cutaneous le ...201627301744
pi inhibits intracellular accumulation of methylglyoxal in promastigote form of l. donovani.similar to their mammalian counterpart, protozoan parasites including leishmania donovani detoxify methylglyoxal (mg),(1) a toxic ubiquitous product generated in glycolysis pathway. however, it differs in one or more way(s) from the humans. it is known that mg is eliminated either through glyoxalase (glo)(2) pathway and/or excreted across the cell membrane. this toxic metabolic by-product is known to be detoxified predominantly by the glo pathway and excretion across the cell membrane is never c ...201627297182
optimization of loop-mediated isothermal amplification (lamp) assays for the detection of leishmania dna in human blood samples.visceral leishmaniasis (vl), one of the most important neglected tropical diseases, is caused by leishmania donovani eukaryotic protozoan parasite of the genus leishmania, the disease is prevalent mainly in the indian sub-continent, east africa and brazil. vl can be diagnosed by pcr amplifying its1 and/or kdna genes. the current study involved the optimization of loop-mediated isothermal amplification (lamp) for the detection of leishmania dna in human blood or tissue samples. three lamp systems ...201627288706
leishmania donovani aurora kinase: a promising therapeutic target against visceral leishmaniasis.aurora kinases are key mitotic kinases executing multiple aspects of eukaryotic cell-division. the apicomplexan homologs being essential for survival, suggest that the leishmania homolog, annotated ldairk, may be equally important.201627288586
integracides h-j: new tetracyclic triterpenoids from the endophytic fungus fusarium sp.three new tetracyclic triterpenoids namely, integracides h (1), i (4), and j (5), along with integracides b (3) and f (2) have been isolated from the endophytic fungus fusarium sp. isolated from the roots of mentha longifolia l. (labiatae) growing in saudi arabia. the structure elucidation of the isolated compounds was achieved by spectroscopic analysis including uv, ir, 1d ((1)h and (13)c) and 2d ((1)h(1)h cosy, tocsy, hsqc, hmbc, and noesy) nmr as well as hresims and comparison with literature ...201627282207
histone acetyltransferase hat4 modulates navigation across g2/m and re-entry into g1 in leishmania donovani.histone acetyltransferases impact multiple processes. this study investigates the role of histone acetyltransferase hat4 in leishmania donovani. though hat4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with hat4-nulls experiencing an unusually long g2/m. survival of hat4-nulls in macrophages was also substantially compromised. dna microarray analysis revealed that hat4 modestly regulated the expression of only a select number of genes, thu ...201627272906
innate immune b cell activation by leishmania donovani exacerbates disease and mediates hypergammaglobulinemia.participation of b cells in the immune response by various antibody-independent mechanisms has recently been uncovered. b cells producing cytokines have been described for several infections and appear to regulate the adaptive immune response. b cell activation by leishmania donovani results in disease exacerbation. how leishmania activates b cells is still unknown. we show that l. donovani amastigotes activate b cells by triggering endosomal tlrs; this activation leads to the induction of vario ...201627264176
a gcn2-like eif2α kinase (ldek1) of leishmania donovani and its possible role in stress response.translation regulation in leishmania parasites assumes significance particularly because they encounter myriad of stresses during their life cycle. the eukaryotic initiation factor 2α (eif2α) kinases, the well-known regulators of translation initiation in higher eukaryotes have now been found to control various processes in these protozoan parasites as well. here, we report on cloning and characterization of a gcn2-like eif2α kinase from l. donovani and also on its modulation during nutrient sta ...201627248816
identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors.a library of arylidenefuropyridinediones was discovered as potent inhibitors of leishmania donovani topoisomerase 1 (ldtop1) where the active molecules displayed considerable inhibition with single digit micromolar ec50 values. this molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. the design was rationalized by molecular docking analysis of the compound prototype with human to ...201627221589
the anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.there is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (vl). we report that delamanid (opc-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of leishmania donovani both in vitro and in vivo. twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of vl. treatment with lower doses revealed a u-shaped (hormetic) dose-response curve with greater parasite ...201627215734
cholesterol corrects altered conformation of mhc-ii protein in leishmania donovani infected macrophages: implication in therapy.previously we reported that kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. splenic macrophages (mφ) of leishmania donovani (ld) infected mice show decrease in membrane cholesterol, while ld infected macrophages (i-mφ) show defective t cell stimulating ability that could be corrected by liposomal delivery of cholesterol. t helper cells recognize peptide antigen in the context of class ii mhc molecule. it is known that the conformation o ...201627214205
detection of leishmania donovani in peripheral blood of asymptomatic individuals in contact with patients with visceral leishmaniasis.the majority of individuals infected with leishmania donovani complex remain asymptomatic. they may act as transmission reservoirs for visceral leishmaniasis (vl). we investigated sero-prevalence of l. donovani complex amongst those closely associated with patients with vl and whether these sero-reactive individuals had leishmania parasites in their peripheral blood. other risk factors were also investigated.201627198212
chemical and antimicrobial profiling of propolis from different regions within libya.extracts from twelve samples of propolis collected from different regions of libya were tested for their activity against trypanosoma brucei, leishmania donovani, plasmodium falciparum, crithidia fasciculata and mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. all the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of ec50 values between 1.65 and 53.6 μg/ml. the toxicity against mammalian cell ...201627195790
purification and characterization of a novel intracellular sucrase enzyme of leishmania donovani promastigotes.the promastigote stage of leishmania resides in the sand fly gut, enriched with sugar molecules. recently we reported that leishmania donovani possesses a sucrose uptake system and a stable pool of intracellular sucrose metabolizing enzyme. in the present study, we purified the intracellular sucrase nearly to its homogeneity and compared it with the purified extracellular sucrase. the estimated size of intracellular sucrase is ~112 kda by gel filtration chromatography, native page, and substrate ...201627190649
elevated serum ada activity as a marker for diagnosis and prognosis of visceral leishmaniasis and post kala-azar dermal leishmaniasis in indian patients.serum adenosine deaminase (ada) activity increases in diseases where cellular immunity is involved. since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ada activity in different pathological conditions. adenosine deaminase was determined in sera of active visceral leishmaniasis (vl) patients (n = 39), active postkala-azar dermal leishmaniasis (pkdl) cases (n = 3 ...201627186641
supplementation of host response by targeting nitric oxide to the macrophage cytosol is efficacious in the hamster model of visceral leishmaniasis and adds to efficacy of amphotericin b.we investigated efficacy of nitric oxide (no) against leishmania donovani. no is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. however, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. we incorporated diethylenetriamine no adduct (deta/no), a prodrug, into poly(lactide-co-glyc ...201627183429
mobile suitcase laboratory for rapid detection of leishmania donovani using recombinase polymerase amplification assay.leishmania donovani (ld) is a protozoan parasite transmitted to humans from sand flies, which causes visceral leishmaniasis (vl). currently, the diagnosis is based on presence of the anti-ld antibodies and clinical symptoms. molecular diagnosis would require real-time pcr, which is not easy to implement at field settings. in this study, we report on the development and testing of a recombinase polymerase amplification (rpa) assay for the detection of ld.201627177926
structure- and ligand-based approaches to evaluate aporphynic alkaloids from annonaceae as multi-target agent against leishmania donovani.leishmaniasis is a neglected disease that affects 15 million people around the world. many limitations are associated to the treatment as high cost and toxicity. several classes of natural substances with proven leishmanicidal activity were reported in the literature. phytochemsitry study of anaxagorea dolichocarpa (annonacea) reported the isolation of aporphine alkaloids.201627174814
sla-pgn-primed dendritic cell-based vaccination induces th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of pkcβ.emergence of drug resistance during visceral leishmaniasis (vl) is a major obstacle imposed during successful therapy. an effective vaccine strategy against this disease is therefore necessary. our present study exploited the sla (soluble leishmanial antigen) and pgn (peptidoglycan) stimulated bone marrow-derived dendritic cells (dcs) as a suitable vaccine candidate during experimental vl. sla-pgn-stimulated dcs showed a significant decrease in hepatic and splenic parasite burden, which were ass ...201627150838
the contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis.leishmania is a genus of protozoan parasites that give rise to a range of diseases called leishmaniasis that affects annually an estimated 1.3 million people from 88 countries. leishmania donovani and leishmania (l.) infantum chagasi are responsible to cause the visceral leishmaniasis. the parasite can use assorted strategies to interfere with the host homeostasis to establish persistent infections that without treatment can be lethal. in this review, we highlight the mechanisms involved in the ...201627148272
development of plga-peg encapsulated miltefosine based drug delivery system against visceral leishmaniasis.targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated plga–peg nanoparticles (ppem) to target macrophage of infected tissues against leishmania donovani. the structural characterization of plga–peg by transmission electron microscopy (tem) has shown a size range of 10 to 15 nm. synthesis and drug encapsulation confirmed by dynamic light scattering (dls) and fourier transform infrared spectrosc ...201626652429
induction of apoptosis by zerumbone isolated from zingiber zerumbet (l.) smith in protozoan parasite leishmania donovani due to oxidative stress.in the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against leishmania infection. various ginger spices of the zingiberaceae family are widely used as spices, flavouring agents, and medicines in southeast asia because of their unique flavour as well as due to their medicinal properties. zerumbone, a natural component of zingiber zerumbet (l.) s ...201626643969
a new bisbenzylisoquinoline alkaloid isolated from thalictrum foliolosum, as a potent inhibitor of dna topoisomerase ib of leishmania donovani.chemical investigation of the stem of thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). the structures of the new compounds were established by detailed 2d nmr spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. inhibitory activities of these four compounds against dna t ...201626625837
establishment of correlation between in-silico and in-vitro test analysis against leishmania hgprt to inhibitors.hypoxanthine phosphoribosyltransferase (hgprt; ec 2.4.2.8) is a central enzyme in the purine recycling pathway of all protozoan parasites. protozoan parasites cannot synthesize purine bases (dna/rna) which is essential for survival as lack of de-novo pathway. thus its good target for drug design and discovery as inhibition leads to cessation of replication. prtase (transferase enzyme) has common prtase type i folding pattern domain for its activities. genomic studies revealed the sequence patter ...201626616453
impaired snx9 expression in immune cells during chronic inflammation: prognostic and diagnostic implications.chronic inflammation is associated with immunosuppression and downregulated expression of the tcr cd247. in searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (snx9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. snx9 expression was affected earlier than cd247 by the generated harmful environment, suggesting that i ...201626608909
il-17a promotes susceptibility during experimental visceral leishmaniasis caused by leishmania donovani.leishmania donovani is an intracellular parasite that infects professional phagocytes and causes visceral leishmaniasis (vl). the immune response during vl has been extensively studied in the context of t-helper (th)1 and th2 responses. immunity against this parasite is dependent on ifn-γ production and subsequent macrophage activation, and the th2 response promotes granuloma formation. the cytokine il-17a is associated with neutrophilic inflammation. depletion of neutrophils during experimental ...201626581600
comparative study of structural models of leishmania donovani and human gdp-mannose pyrophosphorylases.leishmania is the parasite responsible for the neglected disease leishmaniasis. its virulence and survival require biosynthesis of glycoconjugates, whose guanosine diphospho-d-mannose pyrophosphorylase (gdp-mp) is a key player. however, experimentally resolved structures of this enzyme are still lacking. we herein propose structural models of the gdp-mp from human and leishmania donovani. based on a multiple sequences alignment, the models were built with modeller and then carefully refined with ...201626562546
identification and characterization of a leishmania donovani serine protease inhibitor: possible role in regulation of host serine proteases.this study aims to identify, purify, and characterize an endogenous serine protease inhibitor from an indian strain of leishmania donovani, which causes the fatal visceral leishmaniasis.201626656469
leishmania donovani exploits myeloid cell leukemia 1 (mcl-1) protein to prevent mitochondria-dependent host cell apoptosis.apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. in the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (mcl-1) is exploited by the intra-macrophage parasite leishmania donovani to protect their "home" from actinomycin d-induced mitochondria-dependent apoptosis. ...201626670606
leptin induces the phagocytosis and protective immune response in leishmania donovani infected thp-1 cell line and human pbmcs.visceral leishmaniasis (vl) is an infectious disease responsible for several deaths in malnourished children due to impaired cell-mediated immunity, which is accompanied by low circulating leptin levels. the cytokine function of leptin is implicated for several immune regulation activities such as hematopoiesis, angiogenesis, innate and adaptive immunity. its deficiency associated with polarization of th2 response, which coincides with vl pathogenesis. to determine the cytokine role of leptin in ...201626688099
in vitro selection of miltefosine resistance in promastigotes of leishmania donovani from nepal: genomic and metabolomic characterization.in this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (mil) resistance in two clinically derived leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain sb-s; and antimony resistant sb-r). mil-r was easily induced in both strains using the promastigote-stage, but a significant increase in mil-r in the intracellular amastigote compared to the corresponding wild-type did not occur ...201626713880
first evidence of leishmania infection in european brown hare (lepus europaeus) in greece: gis analysis and phylogenetic position within the leishmania spp.although the existence of a sylvatic transmission cycle of leishmania spp., independent from the domestic cycle, has been proposed, data are scarce on leishmania infection in wild mammals in greece. in this study, we aimed to investigate the presence of leishmania infection in the european brown hare in greece, to infer the phylogenetic position of the leishmania parasites detected in hares in greece, and to identify any possible correlation between leishmania infection in hares with environment ...201626386969
protein kinase a signaling during bidirectional axenic differentiation in leishmania.parasitic protozoa of the genus leishmania are obligatory intracellular parasites that cycle between the phagolysosome of mammalian macrophages, where they proliferate as intracellular amastigotes, and the midgut of female sand flies, where they proliferate as extracellular promastigotes. shifting between the two environments induces signaling pathway-mediated developmental processes that enable adaptation to both host and vector. developmentally regulated expression and phosphorylation of prote ...201626460237
exploring the inhibitory activity of withaferin-a against pteridine reductase-1 of l. donovani.withaferin a is an abundant withanolide present in withania somnifera leaves and to some extent in roots. it has been known for its profound anti-cancer properties, but its role in counteracting the leishmania donovani infection has to be explored. pteridine reductase 1 (ptr1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. we employed molecular docking studies to identify the bind ...201626406482
leishmania donovani-specific ub-related modifier-1: an early endosome-associated ubiquitin-like conjugation in leishmania donovani.protein modification by ubiquitin (ub) and ub-like molecules (ubls) is a diverse biological process that regulates the activity of the target proteins. systematic studies of ubls in trypanosomatids like leishmania, the causative organism of potentially fatal visceral leishmaniasis, would yield a better understanding of the disease pathogenesis and identify novel therapeutic targets. the present study is the first to characterize leishmania donovani-specific ub-related modifier-1 (ldurm1) and the ...201626481108
molecular docking and structure-based virtual screening studies of potential drug target, caax prenyl proteases, of leishmania donovani.targeting caax prenyl proteases of leishmania donovani can be a good approach towards developing a drug molecule against leishmaniasis. we have modeled the structure of caax prenyl protease i and ii of l. donovani, using homology modeling approach. the structures were further validated using ramachandran plot and prosa. active site prediction has shown difference in the amino acid residues present at the active site of caax prenyl protease i and caax prenyl protease ii. the electrostatic potenti ...201626551589
short-course treatment regimen of indian visceral leishmaniasis with an indian liposomal amphotericin b preparation (fungisome™).india bears the burden of about half of global visceral leishmaniasis (vl) cases with emerging problems of stibanate resistance. liposomal preparations have improved treatment outcome through shorter duration of therapy and lower toxicity compared with conventional amphotericin b. we report the efficacy of two short-course regimens of an indian preparation of liposomal amphotericin b (fungisome™) for vl caused by leishmania donovani in india. an open-label, randomized, single-center comparative ...201626526926
hepatic stellate cells regulate liver immunity to visceral leishmaniasis through p110δ-dependent induction and expansion of regulatory t cells in mice.visceral leishmaniasis (vl) is associated with severe immune dysfunction and if untreated leads to death. because the liver is one of the primary target organs in vl, unraveling the mechanisms governing the local hepatic immune response is important for understanding the immunopathogenesis of vl. we previously reported that mice with inactivating knockin mutation in the p110δ gene (p110δ(d910a) ) are resistant to vl, due in part to impaired regulatory t-cell (treg) expansion. in this study, we i ...201626289140
antimicrobial and antileishmanial activities of diterpenoids isolated from the roots of salvia deserta.four diterpenes with biological activity were isolated from salvia deserta roots. taxodione was considered leishmanicidal with an ic50 value of 1.46 µm (0.46 mg/l) against leishmania donovani and also exhibited antifungal and antimicrobial activities. ferruginol displayed the greatest activity [24-h ic50 of 4.5 µm (1.29 mg/l)] against the fish pathogenic bacteria streptococcus iniae. the crude extract fraction that contained the isolated compounds 7-o-acetylhorminone and horminone showed stronge ...201626308356
a network map of interleukin-10 signaling pathway.interleukin-10 (il-10) is an anti-inflammatory cytokine with important immunoregulatory functions. it is primarily secreted by antigen-presenting cells such as activated t-cells, monocytes, b-cells and macrophages. in biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer il-10 receptor and induces downstream signaling. il-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as burkitt lymphoma, non-hodgkins lymp ...201626253919
novel inhibitors of ornithine decarboxylase of leishmania parasite (ldodc): the parasite resists ldodc inhibition by overexpression of spermidine synthase.ornithine decarboxylase (ldodc), a key enzyme in polyamine biosynthesis in leishmania donovani, catalyzes the conversion of ornithine to putrescine that is finally used for synthesis of spermidine and other polyamines. inhibition of ornithine decarboxylase is likely to deplete the parasite trypanothione and may result in increased reactive oxygen species (ros). sequence as well as structure of ldodc and human odc shows significant difference; therefore, we have identified novel specific inhibito ...201626362015
bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.kupffer cells (kcs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. recent studies have identified kcs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, ...201627262757
structures and stabilization of kinetoplastid-specific split rrnas revealed by comparing leishmanial and human ribosomes.the recent success in ribosome structure determination by cryoem has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. here, by direct electron-counting cryoem, we have determined the structures of the leishmania donovani and human ribosomes at 2.9 å and 3.6 å, respectively. our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rrna (as ...201627752045
bioprospecting sponge-associated microbes for antimicrobial compounds.sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. however, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. this review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. we discuss the current state-of-the-art by grouping the bioact ...201627144573
recombinant salivary proteins of phlebotomus orientalis are suitable antigens to measure exposure of domestic animals to sand fly bites.certain salivary proteins of phlebotomine sand flies injected into the host skin during blood-feeding are highly antigenic and elicit strong antibody-mediated immune responses in repeatedly-exposed hosts. these antibodies can be measured by enzyme-linked immuno sorbent assays (elisas) using salivary gland homogenates (sghs) as the source of antigens and serve as a markers for exposure to biting sand flies. large-scale screening for anti-sand fly saliva antibodies requires replacement of sgh with ...201626986566
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