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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
potential antileishmanial effect of three medicinal plants.the antileishmanial activity of three organic solvent extracts and water residue of the plants: acacia nilotica (mimosaceae) (husk), ambrosia miratima (astraceae) (aerial shoot) and azadarichta indica (meliaceae) (leaves) were tested in vitro against leishmania donovani promastigotes. the study revealed that the extracts of a. nilotica and a. miratima have effectious antileishmanial activity at concentrations (ic(50)) less than 8 μg/ml, while the extracts of a. indica lack antileishmanial activi ...201223326001
human visceral leishmaniasis in kermanshah province, western iran, during 2011-2012.visceral leishmaniasis (vl) or kala-azar is a parasitic disease caused by the species of leishmania donovani complex. it is endemic in some parts of provinces of iran. according to the reported cases of vl in kermanshah province in recent years, this study was conducted to determine the seroprevalence of vl in high risk villages of the province.201223323091
asymmetric synthesis and anti-protozoal activity of the 8,4'-oxyneolignans virolin, surinamensin and analogues.the asymmetric synthesis of 8,4'-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved. a divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate. in the 15 compounds that were tested, the level of substitution on the a-ring was found to directly influence the activity against leishmania donovani whilst the activity against plasmodium falciparum was influenced by numerous substitution and stereoc ...201223313632
imipramine is an orally active drug against both antimony sensitive and resistant leishmania donovani clinical isolates in experimental infection.in an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. the only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. thus there is a genuine need for an orally active antileishmanial drug. previously it was shown that imipramine, a tricyclic antidepressant alters the proton ...201223301108
a parasite rescue and transformation assay for antileishmanial screening against intracellular leishmania donovani amastigotes in thp1 human acute monocytic leukemia cell line.leishmaniasis is one of the world's most neglected diseases, largely affecting the poorest of the poor, mainly in developing countries. over 350 million people are considered at risk of contracting leishmaniasis, and approximately 2 million new cases occur yearly(1). leishmania donovani is the causative agent for visceral leishmaniasis (vl), the most fatal form of the disease. the choice of drugs available to treat leishmaniasis is limited (2);current treatments provide limited efficacy and many ...201223299097
leishmania donovani develops resistance to drug combinations.drug combinations for the treatment of leishmaniasis represent a promising and challenging chemotherapeutic strategy that has recently been implemented in different endemic areas. however, the vast majority of studies undertaken to date have ignored the potential risk that leishmania parasites could develop resistance to the different drugs used in such combinations. as a result, this study was designed to elucidate the ability of leishmania donovani to develop experimental resistance to anti-le ...201223285310
identification of drosophila gene products required for phagocytosis of leishmania donovani.the identity and function of host factors required for efficient phagocytosis and intracellular maintenance of the protozoan parasite leishmania donovani are poorly understood. utilising the phagocytic capability of drosophila s2 cells, together with available tools for modulating gene expression by rnai, we have developed an experimental system in which to identify host proteins of this type on a genome-wide scale. we have shown that l. donovani amastigotes can be phagocytosed by s2 cells, in w ...201223272175
leishmania donovani zymodeme mon-37 isolated from an autochthonous visceral leishmaniasis patient in sri lanka.although the strain causing cutaneous leishmaniasis (cl) in sri lanka was first identified in 2003, the strain causing visceral leishmaniasis (vl) has not yet been identified. we report the first isoenzyme typing of a strain causing vl in sri lanka at an early stage of emergence of vl in the country. the parasite was isolated from a 57-year-old civil soldier who had been in the jungle in the vavuniya district in the northern province of sri lanka for a period of nearly 6 months immediately befor ...201223265615
apoptotic marker expression in the absence of cell death in staurosporine-treated leishmania donovani.the protozoan parasite leishmania donovani undergoes several developmental transitions in its insect and vertebrate hosts that are induced by environmental changes. the roles of protein kinases in these adaptive differentiation steps and their potential as targets for antiparasitic intervention are only poorly characterized. here, we used the generic protein kinase inhibitor staurosporine to gain insight into how interference with phosphotransferase activities affects the viability, growth, and ...201223263009
vaccine development against leishmania donovani.visceral leishmaniasis (vl) caused by leishmania donovani and leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. zoonotic vl caused by l. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the new world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for res ...201222615707
sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.sialic acids (sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. sialic acid binding immunoglobulins (ig)-like lectins (siglecs) are generally expressed on various immune cells. they selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. many pathogens either synthesize or acquire sialic acids from the host. sialylated pathogens generally use siglecs to manipulate the host immune response. the ...201324434319
leishmania donovani utilize sialic acids for binding and phagocytosis in the macrophages through selective utilization of siglecs and impair the innate immune arm.leishmania donovani, belonging to a unicellular protozoan parasite, display the differential level of linkage-specific sialic acids on their surface. sialic acids binding immunoglobulin-like lectins (siglecs) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with the linkage-specific sialic acids. here we aimed to explore the utilization of sialic acids by leishmania donovani for siglec-mediated binding, phagocytosis, modulation of innate immune response ...201627494323
leishmania promastigotes: building a safe niche within macrophages.upon their internalization by macrophages, leishmania promastigotes inhibit phagolysosome biogenesis. the main factor responsible for this inhibition is the promastigote surface glycolipid lipophosphoglycan (lpg). this glycolipid has a profound impact on the phagosome, causing periphagosomal accumulation of f-actin and disruption of phagosomal lipid microdomains. functionally, this lpg-mediated inhibition of phagosome maturation is characterized by an impaired assembly of the nadph oxidase and t ...201223050244
regulatory actions of toll-like receptor 2 (tlr2) and tlr4 in leishmania donovani infection in the liver.in livers of susceptible but self-curing c57bl/6 mice, intracellular leishmania donovani infection enhanced toll-like receptor 4 (tlr4) and tlr2 gene expression. in the liver, infected tlr4(-/-) mice showed reduced gamma interferon (ifn-γ), tumor necrosis factor (tnf), and inducible nitric oxide synthase (inos) mrna expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of ifn-γ to interleukin 10 (il ...201323589575
the leishmania donovani histidine acid ecto-phosphatase ldmacp: insight into its structure and function.acid ecto-phosphatase activity has been implicated in leishmania donovani promastigote virulence. in the present study, we report data contributing to the molecular/structural and functional characterization of the l. donovani ldmacp (l. donovani membrane acid phosphatase), member of the histidine acid phosphatase (hacp) family. ldmacp is membrane-anchored and shares high sequence identity with the major secreted l. donovani acid phosphatases (ldsacps). sequence comparison of the ldmacp ortholog ...201525695743
downregulation of host tryptophan-aspartate containing coat (taco) gene restricts the entry and survival of leishmania donovani in human macrophage model.leishmania are obligate intracellular protozoan parasites of mammalian hosts. promastigotes of leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. phagosomal maturation arrest is known to play a crucial role in the survival of pathogenic leishmania within activated macrophages. recently, tryptophan-aspartate containing coat (taco) gene has been recognized as playing a central role in the survival of mycobacterium tuberculosi ...201526528242
leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis.gene expression analysis in leishmania donovani (ld) identified an orthologue of the urea cycle enzyme, argininosuccinate synthase (ldass), that was more abundantly expressed in amastigotes than in promastigotes. in order to characterize in detail this newly identified protein in leishmania, we determined its enzymatic activity, subcellular localization in the parasite and affect on virulence in vivo.201223094117
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
identification of leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.visceral leishmaniasis (vl) is a serious lethal parasitic disease caused by leishmania donovani in asia and by leishmania infantum chagasi in southern europe and south america. vl is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. this high incidence is due in part to the lack of an efficacious vaccine. here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with vl. we combi ...201222443237
antimicrobial, anti-inflammatory, antiparasitic, and cytotoxic activities of laennecia confusa.the current paper investigated the potential benefit of the traditional mexican medicinal plant laennecia confusa (cronquist) g. l. nesom (asteraceae). fractions from the hexane, chloroform, methanol, and aqueous extracts were analyzed for antibacterial, antifungal, anti-inflammatory, and antiparasitic activities. the antimicrobial activity of the extracts and fractions was assessed on bacterial and fungal strains, in addition to the protozoa leishmania donovani, using a microdilution assay. the ...201222623891
antimicrobial, antiparasitic, anti-inflammatory, and cytotoxic activities of lopezia racemosa.the present study investigates the potential benefits of the mexican medicinal plant lopezia racemosa (onagraceae). extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. aerial parts of the plant were extracted with various solvents and fractionated accordingly. extracts and fractions were tested against a panel of nine bacterial and four fungal species. the antiparasi ...201323843731
how often do they have sex? a comparative analysis of the population structure of seven eukaryotic microbial pathogens.the model of predominant clonal evolution (pce) proposed for micropathogens does not state that genetic exchange is totally absent, but rather, that it is too rare to break the prevalent pce pattern. however, the actual impact of this "residual" genetic exchange should be evaluated. multilocus sequence typing (mlst) is an excellent tool to explore the problem. here, we compared online available mlst datasets for seven eukaryotic microbial pathogens: trypanosoma cruzi, the fusarium solani complex ...201425054834
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
manipulation of costimulatory molecules by intracellular pathogens: veni, vidi, vici!!some of the most successful pathogens of human, such as mycobacterium tuberculosis (mtb), hiv, and leishmania donovani not only establish chronic infections but also remain a grave global threat. these pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. costimulatory molecul ...201222719245
transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes.the syrian golden hamster (mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants.201425424735
genetically modified live attenuated leishmania donovani parasites induce innate immunity through classical activation of macrophages that direct the th1 response in mice.visceral leishmaniasis (vl) causes significant mortality and there is no effective vaccine. previously, we have shown that genetically modified leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. in this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from balb/c mice both in vitro and in vivo. in vitro infection of macrophages with live ...201526169275
quantifying the contribution of hosts with different parasite concentrations to the transmission of visceral leishmaniasis in ethiopia.an important factor influencing the transmission dynamics of vector-borne diseases is the contribution of hosts with different parasitemia (no. of parasites per ml of blood) to the infected vector population. today, estimation of this contribution is often impractical since it relies exclusively on limited-scale xenodiagnostic or artificial feeding experiments (i.e., measuring the proportion of vectors that become infected after feeding on infected blood/host).201425356795
implication of vector characteristics of phlebotomus argentipes in the kala-azar elimination programme in the indian sub-continent.visceral leishmaniasis (vl), also known as kala-azar in the indian sub-continent (isc), is a major public health concern in bangladesh, india, and nepal, where it is caused by leishmania donovani transmitted by the sand fly phlebotomus argentipes. various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, ph, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. howe ...027376500
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
exposure to leishmania spp. and sand flies in domestic animals in northwestern ethiopia.human visceral leishmaniasis caused by leishmania donovani is considered an anthroponosis; however, leishmania-infected animals have been increasingly reported in l. donovani foci, and the role of these animals as reservoirs for human l. donovani infection remains unclear.201526152578
comparison of bloodmeal digestion and the peritrophic matrix in four sand fly species differing in susceptibility to leishmania donovani.the early stage of leishmania development in sand flies is closely connected with bloodmeal digestion. here we compared various parameters of bloodmeal digestion in sand flies that are either susceptible (phlebotomus argentipes and p. orientalis) or refractory (p. papatasi and sergentomyia schwetzi) to leishmania donovani, to study the effects on vector competence. the volume of the bloodmeal ingested, time of defecation of bloodmeal remnants, timing of formation and degradation of the peritroph ...201526030610
nocturnal periodicity of phlebotomus (larroussius) orientalis (diptera: psychodidae) in an endemic focus of visceral leishmaniasis in northern ethiopia.phlebotomus orientalis is the major vector of the intramacrophage protozoa, leishmania donovani, the etiological agent of visceral leishmaniasis (vl) in northern ethiopia and sudan. the objective of this study was to determine the nocturnal periodicity of p. orientalis in the vl endemic focus of tahtay adiyabo district, northern ethiopia.201525889314
attraction of ethiopian phlebotomine sand flies (diptera: psychodidae) to light and sugar-yeast mixtures (co(2)).visceral leishmaniasis (vl) known as kala-azar is a serious systemic disease caused by leishmania donovani parasites (trypanosomatidae: kinetoplastida). the disease is prevalent in the indian sub-continent, east africa and brazil. in africa, the worst affected regions are in sudan, with an estimated 15,000-20,000 cases annually and ethiopia with 5,000-7,000 cases a year. the main vector of vl in sudan and northern ethiopia is phlebotomus orientalis, a sand fly frequently found in association wit ...201324305038
sergentomyia schwetzi is not a competent vector for leishmania donovani and other leishmania species pathogenic to humans.sand fly species of the genus sergentomyia are proven vectors of reptilian leishmania that are non-pathogenic to humans. however, a consideration of the role of sergentomyia spp. in the circulation of mammalian leishmaniasis appears repeatedly in the literature and the possibility of leishmania transmission to humans remains unclear. here we studied the susceptibility of colonized sergentomyia schwetzi to leishmania donovani and two other leishmania species pathogenic to humans: l. infantum and ...201323786805
seroepidemiology and molecular diversity of leishmania donovani complex in georgia.leishmaniasis includes multiple clinical syndromes, most notably visceral, cutaneous, and mucosal forms. visceral leishmaniasis (vl), also known as kala-azar, is a potentially fatal disease endemic to large parts of africa and asia, and in south-eastern europe (greece, turkey, georgia). visceral leishmaniasis is a parasitic zoonosis caused by species of the l. donovani complex. in the classical epidemiological model the main reservoir for vl are canines.201627177688
phlebotomus orientalis sand flies from two geographically distant ethiopian localities: biology, genetic analyses and susceptibility to leishmania donovani.phlebotomus orientalis parrot (diptera: psychodidae) is the main vector of visceral leishmaniasis (vl) caused by leishmania donovani in east africa. here we report on life cycle parameters and susceptibility to l. donovani of two p. orientalis colonies originating from different sites in ethiopia: a non-endemic site in the lowlands - melka werer (mw), and an endemic focus of human vl in the highlands - addis zemen (az).201323638207
a review of visceral leishmaniasis during the conflict in south sudan and the consequences for east african countries.visceral leishmaniasis (vl), caused predominantly by leishmania donovani and transmitted by both phlebotomus orientalis and phlebotomus martini, is highly endemic in east africa where approximately 30 thousands vl cases are reported annually. the largest numbers of cases are found in sudan - where phlebotomus orientalis proliferate in acacia forests especially on sudan's eastern border with ethiopia, followed by south sudan, ethiopia, somalia, kenya and uganda. long-standing civil war and unrest ...201627549162
heterogeneity of leishmania donovani parasites complicates diagnosis of visceral leishmaniasis: comparison of different serological tests in three endemic regions.diagnostic tests for visceral leishmaniasis that are based on antigens of a single leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. the aim of this study was to investigate and compare the performance of five serological tests, based on different leishmania antigens, in three endemic countries for visceral leishmaniasis. a total number of 231 sera of symptomatic and asymptomatic cases and controls from three endemic regions of visceral le ...201525734336
physiological age structure and leishmania spp. detection in phlebotomus (larroussius) orientalis (parrot, 1936) (diptera: psychodidae) at an endemic focus of visceral leishmaniasis in northern ethiopia.visceral leishmaniasis (vl) caused by leishmania donovani is endemic in northern ethiopia, where p. orientalis is the most important presumed vector. this study was designed to determine the physiological age structure and the occurrence of leishmania infection in the vector of vl in tahtay adiyabo district, northern ethiopia. sand flies were collected using cdc light traps from peridomestic and agricultural fields between may 2011 and april 2012 and p. orientalis females were dissected for age ...201526294920
species composition of phlebotomine sand flies and bionomics of phlebotomus orientalis (diptera: psychodidae) in an endemic focus of visceral leishmaniasis in tahtay adiyabo district, northern ethiopia.visceral leishmaniasis (vl) is a neglected tropical disease, which is strongly associated with poverty. vl caused by leishmania donovani and transmitted by phlebotomus orientalis is endemic in various remote areas of north and north-west ethiopia. the present study was designed to determine the sand fly fauna and bionomics of p. orientalis in the vl endemic focus of tahtay adiyabo district.201525907252
xenodiagnosis of leishmania donovani in balb/c mice using phlebotomus orientalis: a new laboratory model.in areas endemic for visceral leishmaniasis (vl), the majority of infected hosts remain asymptomatic but potentially infectious to biting sand flies. their infectiousness for sand fly vectors is crucial for the transmission of the disease and can be quantified only by xenodiagnosis. however, in the case of human hosts, xenodiagnosis can be problematic for ethical and logistic reasons. the balb/c mouse model described in this paper was designed to enable xenodiagnostic studies on vl hosts circumv ...201525881258
immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease.self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (vl), which is fatal if left untreated. the epidemiology and clinical features of vl vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. human immunodeficiency virus infection augments the severity of vl increasing the risk of developing active disease by 100-2320 times. an effective vacc ...201424982655
comparative analysis of salivary gland transcriptomes of phlebotomus orientalis sand flies from endemic and non-endemic foci of visceral leishmaniasis.in east africa, phlebotomus orientalis serves as the main vector of leishmania donovani, the causative agent of visceral leishmaniasis (vl). phlebotomus orientalis is present at two distant localities in ethiopia; addis zemen where vl is endemic and melka werer where transmission of vl does not occur. to find out whether the difference in epidemiology of vl is due to distant compositions of p. orientalis saliva we established colonies from addis zemen and melka werer, analyzed and compared the t ...201424587463
a new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.visceral leishmaniasis (vl) is transmitted by sand flies. protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for vl.201323288926
kdna genetic signatures obtained by lssp-pcr analysis of leishmania (leishmania) infantum isolated from the new and the old world.visceral leishmaniasis (vl) caused by species from the leishmania donovani complex is the most severe form of the disease, lethal if untreated. vl caused by leishmania infantum is a zoonosis with an increasing number of human cases and millions of dogs infected in the old and the new world. in this study, l. infantum (syn. l.chagasi) strains were isolated from human and canine vl cases. the strains were obtained from endemic areas from brazil and portugal and their genetic polymorphism was ascer ...201222912862
analysis of kinetoplast cytochrome b gene of 16 leishmania isolates from different foci of china: different species of leishmania in china and their phylogenetic inference.leishmania species belong to the family trypanosomatidae and cause leishmaniasis, a geographically widespread disease that infects humans and other vertebrates. this disease remains endemic in china. due to the large geographic area and complex ecological environment, the taxonomic position and phylogenetic relationship of chinese leishmania isolates remain uncertain. a recent internal transcribed spacer 1 and cytochrome oxidase ii phylogeny of chinese leishmania isolates has challenged some asp ...201323383990
exposure to phlebotomus argentipes (diptera, psychodidae, phlebotominae) sand flies in rural areas of bihar, india: the role of housing conditions.visceral leishmaniasis (vl) is a vector-borne infectious disease, caused by the protozoan leishmania donovani, which is transmitted by phlebotomine sand flies. in an earlier study in bihar, india, we found an association between incidence of vl and housing conditions. in the current study we investigated the influence of housing structure and conditions in and around the house on the indoor abundance of phlebotomus argentipes, the vector of vl in this area.201425184542
small rnas derived from trnas and rrnas are highly enriched in exosomes from both old and new world leishmania providing evidence for conserved exosomal rna packaging.leishmania use exosomes to communicate with their mammalian hosts and these secreted vesicles appear to contribute to pathogenesis by delivering protein virulence factors to macrophages. in other eukaryotes, exosomes were found to carry rna cargo, such as mrnas and small non-coding rnas, capable of altering recipient cell phenotype. whether leishmania exosomes also contain rnas which they are able to deliver to bystander cells is not known. here, we show that leishmania exosomes indeed contain r ...201525764986
nocturnal activities and host preferences of phlebotomus orientalis in extra-domestic habitats of kafta-humera lowlands, kala-azar endemic, northwest ethiopia.phlebotomus orientalis feeds on a variety of wild and domestic animals and transmits leishmania donovani from hitherto unknown reservoir hosts to humans in extra-domestic habitats in the metema-humera lowlands. the aim of this study was to determine the nocturnal activities of p. orientalis and its preferred blood meal hosts.201425515239
multilocus sequence and microsatellite identification of intra-specific hybrids and ancestor-like donors among natural ethiopian isolates of leishmania donovani.protozoan parasites of the genus leishmania (kinetoplastida: trypanosomatidae) cause widespread and devastating human diseases. visceral leishmaniasis is endemic in ethiopia where it has also been responsible for fatal epidemics. it is postulated that genetic exchange in leishmania has implications for heterosis (hybrid vigour), spread of virulent strains, resistance to chemotherapeutics, and exploitation of different hosts and vectors. here we analyse 11 natural ethiopian leishmania donovani is ...201424995620
concomitant infection with leishmania donovani and l. major in single ulcers of cutaneous leishmaniasis patients from sudan.in sudan human leishmaniasis occurs in different clinical forms, that is, visceral (vl), cutaneous (cl), mucocutaneous (ml), and post-kala-azar dermal leishmaniasis (pkdl). clinical samples from 69 sudanese patients with different clinical manifestations were subjected to a pcr targeting the cytochrome oxidase ii (coii) gene for leishmania species identification. mixed infections were suspected due to multiple overlapping peaks presented in some sequences of the coii amplicons. cloning these amp ...201424744788
genomic confirmation of hybridisation and recent inbreeding in a vector-isolated leishmania population.although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. the recent experimental demonstration of a sexual cycle in leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still ...201424453988
reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood.depressed cell-mediated immunity in human visceral leishmaniasis (vl) (also known as kala-azar), revealed as the inability of peripheral blood mononuclear cells (pbmcs) to respond to leishmania antigen, remains a hallmark of and is thought to underlie the progressive nature of this disease. we recently reported the ability of a whole-blood, gamma interferon (ifn-γ) release assay to detect subclinical infections among healthy individuals living in an area where kala-azar is endemic (bihar, india) ...201222539471
cutaneous leishmaniasis in a nonendemic area of south rajasthan: a prospective study.cutaneous leishmaniasis (cl) usually occurs in areas with hot and dry climate. in india, the desert areas of rajasthan, gujarat, and the plains of northwestern frontier are endemic for this disorder.027688441
multilocus microsatellite typing (mlmt) of strains from turkey and cyprus reveals a novel monophyletic l. donovani sensu lato group.new foci of human cl caused by strains of the leishmania donovani (l. donovani) complex have been recently described in cyprus and the çukurova region in turkey (l. infantum) situated 150 km north of cyprus. cypriot strains were typed by multilocus enzyme electrophoresis (mlee) using the montpellier (mon) system as l. donovani zymodeme mon-37. however, multilocus microsatellite typing (mlmt) has shown that this zymodeme is paraphyletic; composed of distantly related genetic subgroups of differen ...201222348162
moving from unsequenced to sequenced genome: reanalysis of the proteome of leishmania donovani.the kinetoplastid protozoan parasite, leishmania donovani, is the causative agent of kala azar or visceral leishmaniasis. kala azar is a severe form of leishmaniasis that is fatal in the majority of untreated cases. studies on proteomic analysis of l. donovani thus far have been carried out using homology-based identification based on related leishmania species (l. infantum, l. major and l. braziliensis) whose genomes have been sequenced. recently, the genome of l. donovani was fully sequenced a ...201323665000
do size and insecticide treatment matter? evaluation of different nets against phlebotomus argentipes, the vector of visceral leishmaniasis in nepal.in the indian subcontinent, leishmania donovani, the parasite causing visceral leishmaniasis (vl) is transmitted by the sand fly vector phlebotomus argentipes. long lasting insecticide treated nets (ln) have been postulated as alternative or complement to indoor residual spraying but there are few field studies evaluating the entomological efficacy of different nets against this vector. we conducted two crossover trials in a vl endemic area in nepal to compare the barrier effect of (1) ln with d ...201425494099
epidemiology of visceral leishmaniasis.leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. these parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. this review focuses on the two parasites causing most human visceral leishmaniasis (vl), which leads to substantial health problems or death for up to 400,000 people per year. except for travel cases, leishmania donovani infections are restricted to the (sub-)tropics of ...201424833919
evaluation of pcr procedures for detecting and quantifying leishmania donovani dna in large numbers of dried human blood samples from a visceral leishmaniasis focus in northern ethiopia.visceral leishmaniasis (vl) is a disseminated protozoan infection caused by leishmania donovani parasites which affects almost half a million persons annually. most of these are from the indian sub-continent, east africa and brazil. our study was designed to elucidate the role of symptomatic and asymptomatic leishmania donovani infected persons in the epidemiology of vl in northern ethiopia.201323530965
understanding the transmission dynamics of leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in bihar, india.visceral leishmaniasis (vl) is a neglected vector-borne disease. in india, it is transmitted to humans by leishmania donovani-infected phlebotomus argentipes sand flies. in 2005, vl was targeted for elimination by the governments of india, nepal and bangladesh by 2015. the elimination strategy consists of rapid case detection, treatment of vl cases and vector control using indoor residual spraying (irs). however, to achieve sustained elimination of vl, an appropriate post elimination surveillanc ...201626812963
a novel molecular test to diagnose canine visceral leishmaniasis at the point of care.dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis (vl) but current serological methods are not sensitive enough to detect all subclinically infected animals, which is crucial to vl control programs. polymerase chain reaction (pcr) methods have greater sensitivity but require expensive equipment and trained personnel, impairing its implementation in endemic areas. we developed a diagnostic test that uses isothermal recombinase polymerase amplification (rpa) to detect leish ...201526240156
visceral leishmaniasis on the indian subcontinent: modelling the dynamic relationship between vector control schemes and vector life cycles.visceral leishmaniasis (vl) is a disease caused by two known vector-borne parasite species (leishmania donovani, l. infantum), transmitted to man by phlebotomine sand flies (species: phlebotomus and lutzomyia), resulting in ≈50,000 human fatalities annually, ≈67% occurring on the indian subcontinent. indoor residual spraying is the current method of sand fly control in india, but alternative means of vector control, such as the treatment of livestock with systemic insecticide-based drugs, are be ...201627537774
the potential use of forensic dna methods applied to sand fly blood meal analysis to identify the infection reservoirs of anthroponotic visceral leishmaniasis.in the indian sub-continent, visceral leishmaniasis (vl), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite leishmania donovani and transmitted by the sand fly phlebotomus argentipes. vl is prevalent in northeast india where it is believed to have an exclusive anthroponotic transmission cycle. there are four distinct cohorts of l. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured vl cas ...201627192489
measures to control phlebotomus argentipes and visceral leishmaniasis in india.visceral leishmaniasis is a deadly parasitic disease that is transmitted via the bite of a female sand fly, phlebotomus argentipes. the highest burden of this disease is in northern india. in 2005, india embarked on an initiative with nepal, bangladesh, and the world health organization to eliminate visceral leishmaniasis by 2015. with the goal of 1 case in 10,000 people still unmet, it is prudent to evaluate the tools that have been used thus far to reduce vector numbers and cases of the diseas ...201627308270
leptomonas seymouri: adaptations to the dixenous life cycle analyzed by genome sequencing, transcriptome profiling and co-infection with leishmania donovani.the co-infection cases involving dixenous leishmania spp. (mostly of the l. donovani complex) and presumably monoxenous trypanosomatids in immunocompromised mammalian hosts including humans are well documented. the main opportunistic parasite has been identified as leptomonas seymouri of the sub-family leishmaniinae. the molecular mechanisms allowing a parasite of insects to withstand elevated temperature and substantially different conditions of vertebrate tissues are not understood. here we de ...201526317207
transmission of leishmania donovani in the hills of eastern nepal, an outbreak investigation in okhaldhunga and bhojpur districts.in the indian subcontinent, visceral leishmaniasis is endemic in a geographical area coinciding with the lower gangetic plain, at low altitude. vl occurring in residents of hill districts is therefore often considered the result of leishmania donovani infection during travel. early 2014 we conducted an outbreak investigation in okhaldhunga and bhojpur districts in the nepal hills where increasing number of vl cases have been reported.201526252494
visceral leishmaniasis with roth spots.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani and transmitted by the bite of infected sandfly phlebotomus argentipes. the protozoa is obliged intracellularly and causes a wide spectrum of clinical syndromes: vl ('kala azar'), cutaneous leishmaniasis and mucocutaneous leishmaniasis (espundia). kala azar is the most aggressive form and if untreated causes high mortality. here, we describe a case of vl that presented to us with high-grade fever and found to hav ...201425988048
antimony resistant leishmania donovani but not sensitive ones drives greater frequency of potent t-regulatory cells upon interaction with human pbmcs: role of il-10 and tgf-β in early immune response.in india the sand fly, phlebotomus argentipes, transmitted parasitic disease termed kala-azar is caused by leishmania donovani (ld) in humans. these immune-evading parasites have increasingly developed resistance to the drug sodium antimony gluconate in endemic regions. lack of early diagnosis methods for the disease limits the information available regarding the early interactions of this parasite with either human tissues or cell lineages. we reasoned that peripheral blood mononuclear cells (p ...201425032977
nucleosomal histone proteins of l. donovani: a combination of recombinant h2a, h2b, h3 and h4 proteins were highly immunogenic and offered optimum prophylactic efficacy against leishmania challenge in hamsters.the present study includes cloning and expression of recombinant leishmania donovani histone proteins (rldh2b, rldh3, rldh2a and rldh4), assessment of their immunogenicity in leishmania infected cured patients/endemic contacts as well as in cured hamsters and finally evaluation of their prophylactic efficacy in hamsters against l. donovani challenge. all recombinant proteins were expressed and purified from the heterologous bacterial host system. leishmania infected cured patients/endemic contac ...201424926878
significantly lower anti-leishmania igg responses in sudanese versus indian visceral leishmaniasis.visceral leishmaniasis (vl), a widely distributed systemic disease caused by infection with the leishmania donovani complex (l. donovani and l. infantum), is almost always fatal if symptomatic and untreated. a rapid point-of-care diagnostic test for anti-leishmania antibodies, the rk39-immunochromatographic test (rk39-ict), has high sensitivity and specificity in south asia but is less sensitive in east africa. one of the underlying reasons may be continent-specific molecular diversity in the rk ...201424587456
risk factors for visceral leishmaniasis and asymptomatic leishmania donovani infection in india and nepal.there is increasing interest in the role of asymptomatic infection in transmission of visceral leishmaniasis (vl). we studied the individual, household and environmental factors associated with asymptomatic leishmania donovani infected individuals and vl. 7,538 individuals living in vl endemic villages in india and nepal were divided into three mutually exclusive groups based on their vl history and direct agglutination test (dat) results in yearly serosurveys over a two-year period. the groups ...201424498159
cross-sectional study to assess risk factors for leishmaniasis in an endemic region in sri lanka.sri lanka reports significantly more cutaneous leishmaniasis (cl) cases than visceral leishmaniasis (vl) cases, both of which are caused by leishmania donovani mon-37. a cross-sectional study conducted in an area with a high prevalence of cl prevalent included 954 participants of an estimated population of 61,674 to estimate the number of cl cases, ascertain whether there is a pool of asymptomatic vl cases, and identify risk factors for transmission. a total of 31 cases of cl were identified, of ...201323918217
seasonal variation in the prevalence of sand flies infected with leishmania donovani.visceral leishmaniasis (vl) is a life threatening neglected infectious disease in the indian subcontinent, transmitted by the bite of female sand flies. estimation of the infectivity in the vector population, collected in different seasons, may be useful to better understanding the transmission dynamics of vl as well as to plan vector control measures.201323585896
solid™ sequencing of genomes of clinical isolates of leishmania donovani from india confirm leptomonas co-infection and raise some key questions.known as 'neglected disease' because relatively little effort has been applied to finding cures, leishmaniasis kills more than 150,000 people every year and debilitates millions more. visceral leishmaniasis (vl), also called kala azar (ka) or black fever in india, claims around 20,000 lives every year. whole genome analysis presents an excellent means to identify new targets for drugs, vaccine and diagnostics development, and also provide an avenue into the biological basis of parasite virulence ...201323418454
low prevalence of leishmania donovani infection among the blood donors in kala-azar endemic areas of bangladesh.visceral leishmaniasis (vl) is a major public health problem in bangladesh with the highest disease burden in the mymensingh district. the disease is transmitted by sand fly bites, but it may also be transmitted through blood transfusions. no information is available about the prevalence of leishmania infection among blood donors in bangladesh; therefore we aimed to investigate this question.201323375008
an outbreak investigation of visceral leishmaniasis among residents of dharan town, eastern nepal, evidence for urban transmission of leishmania donovani.visceral leishmaniasis (vl) is a predominantly rural disease, common in the low lands of eastern nepal. since 1997 vl cases have also been reported among residents of the city of dharan. our main research objective was to find out whether there had been local transmission of vl inside the city.201323327548
immunobiology of visceral leishmaniasis.visceral leishmaniasis (vl), commonly known as kala-azar, is caused by leishmania donovani and leishmania infantum (leishmania chagasi in the americas). these leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver, and bone marrow. patients with active disease typically exhibit marked immunosuppression, lack reactivity to the leishmania skin test (lst), a delayed type hypersensitivity test, and their peripheral blood mononuclear cells ...201222912637
prevalence of sand flies and leishmania donovani infection in a natural population of female phlebotomus argentipes in bihar state, india.leishmaniasis is a vector-borne disease, and in the indian subcontinent the female phlebotomus argentipes is the vector for leishmania donovani. however, data on the extent of sand fly infection rates in natural settings using molecular methods have not been extensively reported in india. in this study a pcr technique was applied targeting the 18s rrna encoding region to determine the prevalence of leishmania infection in female p. argentipes captured in the field. for this study, sand flies wer ...201222217179
in vitro permissiveness of bovine neutrophils and monocyte derived macrophages to leishmania donovani of ethiopian isolate.epidemiological studies in ethiopia have documented that the risk of visceral leishmaniasis (vl, kala-azar) is higher among people living with domestic animals. the recent report on isolation of leishmania donovani complex dna and the detected high prevalence of anti-leishmanial antibodies in the blood of domestic animals further strengthen the potential role of domestic animals in the epidemiology of vl in ethiopia. in mammalian hosts polymorphonuclear cells (pmn) and macrophages are the key im ...201627090082
host-feeding preference of phlebotomus orientalis (diptera: psychodidae) in an endemic focus of visceral leishmaniasis in northern ethiopia.blood-feeding behavior studies are important for estimating the efficiency of pathogen transmission and assessing the relative human disease risk. however, in ethiopia and other parts of east africa there are large remaining gaps in identifying the feeding habits of phlebotomus orientalis, the vector of leishmania donovani. the aim of the study was to determine the blood feeding patterns of p. orientalis in tahtay adiyabo district, northern ethiopia.201525963759
sero-prevalence of leishmania donovani infection in labour migrants and entomological risk factors in extra-domestic habitats of kafta-humera lowlands - kala-azar endemic areas in the northwest ethiopia.visceral leishmaniasis (vl) or kala-azar cases in seasonal labour migrants from highland areas are addressed to travel history to the metema-humera lowlands, northwestern ethiopia. factors that affect the incidence of vl in extra-domestic habitats were not evaluated. the aim of this study was to evaluate sero-prevalence of leishmania donovani infection in randomly selected labour migrant workers and entomological risk factors which might affect the incidence of kala-azar.201525884167
polymorphism in the haspb repeat region of east african leishmania donovani strains.visceral leishmaniasis (vl) caused by leishmania donovani is a major health problem in ethiopia. parasites in disparate regions are transmitted by different vectors, and cluster in distinctive genotypes. recently isolated strains from vl and hiv-vl co-infected patients in north and south ethiopia were characterized as part of a longitudinal study on vl transmission.201323358849
pharmacological assessment defines leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.protein kinase inhibitors have emerged as new drugs in various therapeutic areas, including leishmaniasis, an important parasitic disease. members of the leishmania casein kinase 1 (ck1) family represent promising therapeutic targets. leishmania casein kinase 1 isoform 2 (ck1.2) has been identified as an exokinase capable of phosphorylating host proteins, thus exerting a potential immune-suppressive action on infected host cells. moreover, its inhibition reduces promastigote growth. despite thes ...201324366737
targeting lysine deacetylases (kdacs) in parasites.due to an increasing problem of drug resistance among almost all parasites species ranging from protists to worms, there is an urgent need to explore new drug targets and their inhibitors to provide new and effective parasitic therapeutics. in this regard, there is growing interest in exploring known drug leads of human epigenetic enzymes as potential starting points to develop novel treatments for parasitic diseases. this approach of repurposing (starting with validated targets and inhibitors) ...201526402733
a unique modification of the eukaryotic initiation factor 5a shows the presence of the complete hypusine pathway in leishmania donovani.deoxyhypusine hydroxylase (dohh) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (n(€)-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5a (eif5a). we present here the molecular and structural basis of the function of dohh from the protozoan parasite, leishmania donovani, which causes visceral leishmaniasis. the l. donovani dohh gene is 981 bp and encodes a putative polypeptide of 326 amin ...201222438895
drug resistance in natural isolates of leishmania donovani s.l. promastigotes is dependent of pgp170 expression.resistance of pathogens to drugs is a growing concern regarding many diseases. parasites like leishmania, plasmodium and entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. the acquired resistance of leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. to test the hypothesis that drug efflux in leishmania, as measured by flow cytometry using the fluoresce ...201323776486
highlights on molecular identification of closely related species.the term "complex" emerged in the literature at the beginning of the genomic era associated to taxonomy and grouping organisms that belong to different species but exhibited similar patterns according to their morphological, physiological and/or other phenotypic features. dna-dna hybridization values ~70% and high identity on 16s rrna gene sequences were recommended for species delineation. electrophoretic methods showed in some cases to be useful for species identification and population struct ...201322982158
tick-borne infections of animals and humans: a common ground.a wide variety of pathogens is transmitted from ticks to vertebrates including viruses, bacteria, protozoa and helminths, of which most have a life cycle that requires passage through the vertebrate host. tick-borne infections of humans, farm and companion animals are essentially associated with wildlife animal reservoirs. while some flying insect-borne diseases of humans such as malaria, filariasis and kala azar caused by leishmania donovani target people as their main host, major tick-borne in ...201424846527
molecular and serological detection of tick-borne pathogens in dogs from an area endemic for leishmania infantum in mato grosso do sul, brazil.tick-borne pathogens affect a wide range of vertebrate hosts. to identify tick-borne pathogens among dogs from campo grande, ms, brazil testing seropositive for leishmania infantum (syn. l. chagasi), a serological and molecular study was conducted to detect ehrlichia canis, anaplasma platys and babesia vogeli in 60 serum and spleen samples. a confirmatory diagnosis of l. infantum based on serological and molecular assays was also performed, as was sequence alignment and phylogenetic analysis to ...201424473877
isolation, characterization and antimicrobial evaluation of a novel compound n-octacosan 7β ol, from fumaria parviflora lam.fumaria parviflora lam. (fumaraceae) is widely used in traditional as well as folkloric system of medicine from ancient. it is commonly known as 'pitpapra' or 'shahtrah' in indian traditional system of medicine and used for treating numerous ailments like diarrhea, fever, influenza, blood purifier and other complications. the object of the present study was to evaluate the antileishmanial, antibacterial, antifungal and cytotoxic potential of isolated compound.201424621260
terrenolide s, a new antileishmanial butenolide from the endophytic fungus aspergillus terreus.terrenolide s, a new butenolide derivative (6), together with six known compounds: (22e,24r)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin a (4), terretonin (5) and butyrolactone vi (7) have been isolated from the endophytic fungus aspergillus terreus isolated from the roots of carthamus lanatus (asteraceae). their structures were established by extensive spectroscopic analyses (1d, 2d nmr and hresims), as well as optical rotati ...201626299734
antitrypanosomal alkaloids from the marine bacterium bacillus pumilus.fractionation of the ethyl acetate extract of the marine bacterium bacillus pumilus isolated from the black coral antipathes sp. led to the isolation of five compounds: cyclo-(l-leu-l-pro) (1), 3-hydroxyacetylindole (2), n-acetyl-β-oxotryptamine (3), cyclo-(l-phe-l-pro) (4), and 3-formylindole (5). the structures of compounds 1-5 were established by spectroscopic analyses, including hresitof-ms and nmr (1h, 13c, hsqc, hmbc and cosy). compounds 2, 3 and 5 caused the inhibition on the growth of tr ...201222990456
eleven microbial metabolites of 6-hydroxyflavanone.6-hydroxyflavanone (1) when fermented with fungal culture cunninghamella blakesleeana (atcc 8688a) yielded flavanone 6-o-β-d-glucopyranoside (2), flavanone 6-sulfate (3), and 6-hydroxyflavanone 7-sulfate (4). aspergillus alliaceus (atcc 10060) also transformed 1 to metabolite 3 as well as 4'-hydroxyflavanone 6-sulfate (5) and 6,4'-dihydroxyflavanone (6). beauveria bassiana (atcc 7159) metabolized 1 to 6 and flavanone 6-o-β-d-4-o-methyglucopyranoside (7). mucor ramannianus (atcc 9628) transformed ...201526235165
the narrow active-site cleft of o-acetylserine sulfhydrylase from leishmania donovani allows complex formation with serine acetyltransferases with a range of c-terminal sequences.cysteine is a crucial substrate for the synthesis of glutathione and trypanothione, which in turn maintain intracellular redox homeostasis and defend against oxidative stress in the pathogen leishmania donovani. here, the identification, sequencing, characterization and crystal structure at 1.79 å resolution of o-acetylserine sulfhydrylase (oass), a cysteine-biosynthetic pathway enzyme from l. donovani (ldoass), are reported. it shows binding to the serine acetyltransferase (sat) c-terminal pept ...201222868756
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