Displaying publications 1 - 20 of 35 in total

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  1. Humanizing glycosylation pathways in eukaryotic expression systems
    Khan AH, Bayat H, Rajabibazl M, Sabri S, Rahimpour A
    World J Microbiol Biotechnol, 2017 Jan;33(1):4.
    PMID: 27837408
    Glycosylation represents the most widespread posttranslational modifications, found in a broad spectrum of natural and therapeutic recombinant proteins. It highly affects bioactivity, site-specificity, stability, solubility, immunogenicity, and serum half-life of glycoproteins. Numerous expression hosts including yeasts, insect cells, transgenic plants, and mammalian cells have been explored for synthesizing therapeutic glycoproteins. However, glycosylation profile of eukaryotic expression systems differs from human. Glycosylation strategies have been proposed for humanizing the glycosylation pathways in expression hosts which is the main theme of this review. Besides, we also highlighted the glycosylation potential of protozoan parasites by emphasizing on the mammalian-like glycosylation potential of Leishmania tarentolae known as Leishmania expression system.
    Matched MeSH terms: Leishmania/metabolism
  2. Identification and characterization of Leishmania amastigote and axenic form antigens
    Abdelhaleem AA, Elamin EM, Bakheit SM, Mukhtar MM
    Trop Biomed, 2019 Dec 01;36(4):866-873.
    PMID: 33597459
    This study was aimed to identify and characterize Leishmania amastigote, and axenic form antigens. Two in vitro techniques were used to change leishmania parasite isolates from promastigote form to amastigotes and amastigote like (axenic) forms. The main strategy relied upon in vitro infection of murine macrophages cell line J774 with leishmania promastigote, at 37°C with 5% CO2, while the second technique relied upon the culture of promastigote at 37°C with low pH (5.5), and 5-10% CO2. Proteins were extracted and fractionated utilizing 12% Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS PAGE). Antigens were recognized using both immune dot blot and western blot procedures. PCR was performed for recognition of leishmania parasites in infected J774 macrophages. L. major was quicker in infectivity of macrophages cell line than L. donovani. Shared proteins ranging from 26-116 kDa were identified by SDS PAGE in all stages. Immune Dot-blot method showed positive outcomes, while western blot identified an exceptional antigen band of 16 kDa in amastigote, this unique band could be of value in diagnosis and vaccination of leishmaniasis. PCR results confirmed presence of both isolates demonstrating that coinfection is conceivable, and no indications of hereditary recombination at kinetoplast DNA (kDNA) were identified in macrophages simultaneously infected by L. major and L. donovani.
    Matched MeSH terms: Leishmania/immunology; Leishmania/isolation & purification*; Leishmania donovani; Leishmania major
  3. Evaluation of the in vitro antileishmanial activities of bioactive guided fractionations of two medicinal plants
    Al Nasr IS
    Trop Biomed, 2020 Mar 01;37(1):15-23.
    PMID: 33612714
    The organisms of the genus Leishmania are flagellated protozoan parasites and are the causative agents of leishmaniasis. This disease is a major health problem, especially in tropical countries. Currently, cutaneous leishmaniasis is treated by chemotherapy using pentavalent antimonials, but these drugs have serious organo-toxicity, drug resistance on several occasions, and low efficiency in controlling the infection. The present work is carried out to evaluate the in vitro antileishmanial activity of methanolic extracts and phytochemical fractions of two plants ethnobotanically used against leishmaniasis and skin infection, Calotropis procera and Rhazya stricta leaves against Leishmania major promastigote and amastigote stages and cytotoxicity against the Vero cell line. The leaves of C. procera and R. stricta were extracted with methanol and fractionated by petroleum ether, chloroform, ethyl acetate, n-butanol, and water. The methanolic extracts of the leaves of C. procera and R. stricta exhibited antileishmanial activity against L. major promastigotes with IC50 values of 66.8 and 42.4 µg mL-1, respectively. While their CC50 2.3 and 298 µg mL-1 and their SI 0.03 and 7.03 respectively. However, the fractionations of the methanolic extract of C. procera leaves revealed antiparasitic activity against both L. major promastigote and amastigote stages in vitro, which significantly increased with polarity with the exception of n-butanol. Hence the best activity was revealed by the water fraction (IC50 of 26.3 and 29.0 µg mL-1) for the two stages. In conclusion, further phytochemical investigation should be performed for the C. procera water extract in terms of antileishmanial active ingredient isolation that may enhance the possibility of avoiding toxic substances and overcome the low SI (1.1 and 1.01).
    Matched MeSH terms: Leishmania major/drug effects*
  4. Efficacy of pentamidine-loaded chitosan nanoparticles as a novel drug delivery system for Leishmania tropica
    Khan RU, Khan M, Sohail A, Ullah R, Iqbal A, Ahmad B, et al.
    Trop Biomed, 2022 Dec 01;39(4):511-517.
    PMID: 36602209 DOI: 10.47665/tb.39.4.003
    The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles (PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate (TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture, zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910 µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however, its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug delivery system. However, further research is needed to support its efficacy in animal and human CL.
    Matched MeSH terms: Leishmania tropica*
  5. Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection
    Majeed QA, Alshammari A, Alanazi AD
    Trop Biomed, 2023 Jun 01;40(2):259-265.
    PMID: 37650415 DOI: 10.47665/tb.40.2.019
    Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.
    Matched MeSH terms: Leishmania major*
  6. A case report of an uncommon presentation of cutaneous leishmaniasis: A nose lesion
    Alamin AA, Gebreyesus MW, Mohamed I
    Trop Biomed, 2023 Jun 01;40(2):250-252.
    PMID: 37650413 DOI: 10.47665/tb.40.2.017
    Leishmaniasis is a widely spread zoonotic disease caused by the bite of infected sandflies, particularly in developing countries. Cutaneous leishmaniasis can have a diverse range of presentations, ranging from minor skin nodules to significant mucosal damage. However, nose involvement is infrequent. Our report highlights a 15-year-old female patient with a persistent skin lesion on her nose for three months, which is a rare manifestation of cutaneous leishmaniasis. The lesion started as a raised spot with a brownish-red color and a crust but eventually developed into an ulcer that spread over the entire lobe of the nose and even moved toward the eye. Microscopic examination revealed the presence of Leishmania amastigotes, and a biopsy confirmed a diagnosis of cutaneous leishmaniasis. The patient received daily intravenous sodium stibogluconate doses of 9 mg/kg for 20 days, and three weeks later, there was a significant clinical improvement, with the ulcer beginning to heal and no more amastigotes visible on microscopic examination. It is crucial to keep cutaneous leishmaniasis in mind as a possible diagnosis for patients with skin lesions, even in regions where the condition is not prevalent.
    Matched MeSH terms: Leishmania*
  7. Assessment of Euphorbia retusa and Pulicaria undulata activity against Leishmania major and Toxoplasma gondii
    Khan TA, Al Nasr IS, Mujawah AH, Koko WS
    Trop Biomed, 2021 Mar 01;38(1):135-141.
    PMID: 33797536 DOI: 10.47665/tb.38.1.023
    Leishmaniasis and toxoplasmosis are parasitic protozoal diseases that pose serious health concerns, especially for immunocompromised people. Leishmania major and Toxoplasma gondii are endemic in Saudi Arabia and are particularly common in the Qassim Region. The present work was conducted to evaluate the in vitro antileishmanial and antitoxoplasmal activity of methanolic extracts and phytochemical fractions from two plants, Euphorpia retusa and Pulicaria undulata, which are ethnobotanical agents used to treat parasitic infection. Whole E. retusa and P. undulata plants were extracted with methanol and fractionated using petroleum ether, chloroform, ethyl acetate, n-butanol, and water and then were tested in vitro against L. major promastigote and the amastigote stages of T. gondii; the cytotoxicity of the extracts was tested against Vero cell line. The methanolic extracts of E. retusa and P. undulata exhibited promising antitoxoplasmal activity against T. gondii with EC50 values 5.6 and 12.7 μg mL-1, respectively. The chloroform fraction of P. undulata was the most potent, exhibiting an EC50 of 1.4 μg mL-1 and SI value of 12.1. It was also the most active fraction against both L. major promastigotes and amastigotes, exhibiting an EC50 of 3.9 and 3.8 μg mL-1 and SI values 4.4 and 4.5, respectively. The chloroform fraction from P. undulata is a very good candidate for the isolation of active antitoxoplasmal and antileishmanial ingredients; therefore, further phytochemical analysis for active compound isolation is highly recommended.
    Matched MeSH terms: Leishmania major/drug effects*
  8. DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice
    Maspi N, Ghaffarifar F, Sharifi Z, Dalimi A, Khademi SZ
    Malays J Pathol, 2017 Dec;39(3):267-275.
    PMID: 29279589
    Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis. The aim of the present study was to compare the immune responses induced following DNA vaccination with LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genes alone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immune responses were evaluated before and after challenge with Leishmania major (L. major). In addition, the mean lesion size was also measured from 3th week post-infection. All immunized mice showed a partial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levels compared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstrated the highest IFN-γ and IgG2a levels in the group receiving LACK-TSA fusion. Mean lesion sizes reduced significantly in all immunized mice compared with control groups at 7th week post-infection (p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA and TSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunization promoted Th1 immune response and confirmed the previous observations on immunogenicity of LACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccine can induce stronger immune responses and protection against infectious challenge with L. major.
    Matched MeSH terms: Leishmania major
  9. Fulltext A Review of Quercus infectoria (Olivier) Galls as a Resource for Anti-parasitic Agents: In Vitro and In Vivo Studies
    Zin NNINM, Rahimi WNAWM, Bakar NA
    Malays J Med Sci, 2019 Nov;26(6):19-34.
    PMID: 31908584 MyJurnal DOI: 10.21315/mjms2019.26.6.3
    Parasitic diseases represent one of the causes for significant global economic, environmental and public health impacts. The efficacy of currently available anti-parasitic drugs has been threatened by the emergence of single drug- or multidrug-resistant parasite populations, vector threats and high cost of drug development. Therefore, the discovery of more potent anti-parasitic drugs coming from medicinal plants such as Quercus infectoria is seen as a major approach to tackle the problem. A systematic review was conducted to assess the efficacy of Q. infectoria in treating parasitic diseases both in vitro and in vivo due to the lack of such reviews on the anti-parasitic activities of this plant. This review consisted of intensive searches from three databases including PubMed, Science Direct and Scopus. Articles were selected throughout the years, limited to English language and fully documented. A total of 454 potential articles were identified, but only four articles were accepted to be evaluated based on inclusion and exclusion criteria. Although there were insufficient pieces of evidence to account for the efficacy of Q. infectoria against the parasites, this plant appears to have anti-leishmanial, anti-blastocystis and anti-amoebic activities. More studies in vitro and in vivo are warranted to further validate the anti-parasitic efficacy of Q. infectoria.
    Matched MeSH terms: Leishmania
  10. β-Sitosterol from Ifloga spicata (Forssk.) Sch. Bip. as potential anti-leishmanial agent against leishmania tropica: Docking and molecular insights
    Majid Shah S, Ullah F, Ayaz M, Sadiq A, Hussain S, Ali Shah AU, et al.
    Steroids, 2019 08;148:56-62.
    PMID: 31085212 DOI: 10.1016/j.steroids.2019.05.001
    The current study was aimed to evaluate the anti-leishmanial potentials of β-sitosterol isolated from Ifloga spicata. The anti-leishmanial potential of β-sitosterol is well documented against Leishmania donovani and Leishmania amazonensis but unexplored against Leishmania tropica. Structure of the compound was elucidated by FT-IR, mass spectrometry and multinuclear (1H and 13C) magnetic resonance spectroscopy. The compound was evaluated for its anti-leishmanial potentials against L. tropica KWH23 using in vitro anti-promastigote, DNA interaction, apoptosis, docking studies against leishmanolysin (GP63) and trypanothione reductase (TR) receptors using MOE 2016 software. β-sitosterol exhibited significant activity against leishmania promastigotes with IC50 values of 9.2 ± 0.06 μg/mL. The standard drug glucantaime showed IC50 of 5.33 ± 0.07 µg/mL. Further mechanistic studies including DNA targeting and apoptosis induction via acridine orange assay exhibited promising anti-leishmanial potentials for β-sitosterol. Molecular docking with leishmanolysin (GP63) and trypanothione reductase (TR) receptors displayed the binding scores of β-sitosterol with targets TR and GP63 were -7.659 and -6.966 respectively. The low binding energies -61.54 (for TR) and -33.24 (for GP63) indicate that it strongly bind to the active sites of target receptors. The results confirmed that β-sitosterol have considerable anti-leishmanial potentials and need further studies as potential natural anti-leishmanial agent against L. tropica.
    Matched MeSH terms: Leishmania tropica/drug effects*
  11. Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
    Fazia Adyani Ahmad Fuad, Houston Douglas R, Michels Paul AM, Fothergill-gilmore Linda A, Walkinshaw Malcolm D
    Sains Malaysiana, 2016;45:1113-1120.
    Cofactor-independent phosphoglycerate mutase has been proposed as a therapeutic target for the treatment of
    trypanosomatid diseases. In this paper, we report the identification of compounds that could potentially be developed as
    selective inhibitors of cofactor-independent phosphoglycerate mutase from Leishmania mexicana (LmiPGAM). Virtual
    screening was used in this search, as well as compounds identified by high-throughput screening. A ligand-based virtual
    screen programme, ultra fast shape recognition with atom types (UFSRAT), was used to screen for compounds resembling
    the substrate/product, before a structure-based approach was applied using AutoDock 4 and AutoDock Vina in a consensus
    docking scheme. In this way eight selected compounds were identified. In addition, three compounds from the Library of
    Pharmacologically Active Compounds (LOPAC) were selected from the published results of high-throughput screening of
    this library. The inhibitory effects of these compounds were tested at a fixed concentration of 1 mM. The results showed
    that seven compounds inhibited LmiPGAM activity and of these, two compounds (one each from high-throughput and
    virtual screening) showed substantial inhibition (i.e. 14% and 49% remaining activity, respectively). Taken together, the
    findings from this study indicate that these compounds have potential as novel inhibitors that specifically target LmiPGAM.
    Matched MeSH terms: Leishmania mexicana
  12. Fulltext Molecular characterization of Leishmania species isolated from cutaneous leishmaniasis in Yemen
    Mahdy MA, Al-Mekhlafi HM, Al-Mekhlafi AM, Lim YA, Bin Shuaib NO, Azazy AA, et al.
    PLoS One, 2010 Sep 20;5(9).
    PMID: 20862227 DOI: 10.1371/journal.pone.0012879
    BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in the tropics and subtropics with a global yearly incidence of 1.5 million. Although CL is the most common form of leishmaniasis, which is responsible for 60% of DALYs lost due to tropical-cluster diseases prevalent in Yemen, available information is very limited.

    METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted to determine the molecular characterization of Leishmania species isolated from human cutaneous lesions in Yemen. Dermal scrapes were collected and examined for Leishmania amastigotes using the Giemsa staining technique. Amplification of the ribosomal internal transcribed spacer 1(ITS-1) gene was carried out using nested PCR and subsequent sequencing. The sequences from Leishmania isolates were subjected to phylogenetic analysis using the neighbor-joining and maximum parsimony methods. The trees identified Leishmania tropica from 16 isolates which were represented by two sequence types.

    CONCLUSIONS/SIGNIFICANCE: The predominance of the anthroponotic species (i.e. L. tropica) indicates the probability of anthroponotic transmission of cutaneous leishmaniasis in Yemen. These findings will help public health authorities to build an effective control strategy taking into consideration person-to-person transmission as the main dynamic of transmission of CL.

    Matched MeSH terms: Leishmania/classification; Leishmania/genetics*; Leishmania/isolation & purification*; Leishmaniasis, Cutaneous/epidemiology; Leishmaniasis, Cutaneous/parasitology*
  13. Fulltext First Molecular Characterization of Leishmania Species Causing Visceral Leishmaniasis among Children in Yemen
    Mahdy MA, Al-Mekhlafi AM, Abdul-Ghani R, Saif-Ali R, Al-Mekhlafi HM, Al-Eryani SM, et al.
    PLoS One, 2016;11(3):e0151265.
    PMID: 26966902 DOI: 10.1371/journal.pone.0151265
    Visceral leishmaniasis (VL) is a debilitating, often fatal disease caused by Leishmania donovani complex; however, it is a neglected tropical disease. L. donovani complex comprises two closely related species, L. donovani that is mostly anthroponotic and L. infantum that is zoonotic. Differentiation between these two species is critical due to the differences in their epidemiology and pathology. However, they cannot be differentiated morphologically, and their speciation using isoenzyme-based methods poses a difficult task and may be unreliable. Molecular characterization is now the most reliable method to differentiate between them and to determine their phylogenetic relationships. The present study aims to characterize Leishmania species isolated from bone marrows of Yemeni pediatric patients using sequence analysis of the ribosomal internal transcribed spacer-1 (ITS1) gene. Out of 41 isolates from Giemsa-stained bone marrow smears, 25 isolates were successfully amplified by nested polymerase chain reaction and sequenced in both directions. Phylogenetic analysis using neighbor joining method placed all study isolates in one cluster with L. donovani complex (99% bootstrap). The analysis of ITS1 for microsatellite repeat numbers identified L. infantum in 11 isolates and L. donovani in 14 isolates. These data suggest the possibility of both anthroponotic and zoonotic transmission of VL-causing Leishmania species in Yemen. Exploring the possible animal reservoir hosts is therefore needed for effective control to be achieved.
    Matched MeSH terms: Leishmania donovani/classification; Leishmania donovani/genetics*; Leishmania donovani/isolation & purification; Leishmania infantum/classification; Leishmania infantum/genetics*; Leishmania infantum/isolation & purification
  14. Fulltext Indirect ELISA based on Hendra and Nipah virus proteins for the detection of henipavirus specific antibodies in pigs
    Fischer K, Diederich S, Smith G, Reiche S, Pinho Dos Reis V, Stroh E, et al.
    PLoS One, 2018;13(4):e0194385.
    PMID: 29708971 DOI: 10.1371/journal.pone.0194385
    Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus in the family Paramyxoviridae. Henipavirus infections were first reported in the 1990's causing severe and often fatal outbreaks in domestic animals and humans in Southeast Asia and Australia. NiV infections were observed in humans in Bangladesh, India and in the first outbreak in Malaysia, where pigs were also infected. HeV infections occurred in horses in the North-Eastern regions of Australia, with singular transmission events to humans. Bats of the genus Pteropus have been identified as the reservoir hosts for henipaviruses. Molecular and serological indications for the presence of henipa-like viruses in African fruit bats, pigs and humans have been published recently. In our study, truncated forms of HeV and NiV attachment (G) proteins as well as the full-length NiV nucleocapsid (N) protein were expressed using different expression systems. Based on these recombinant proteins, Enzyme-linked Immunosorbent Assays (ELISA) were developed for the detection of HeV or NiV specific antibodies in porcine serum samples. We used the NiV N ELISA for initial serum screening considering the general reactivity against henipaviruses. The G protein based ELISAs enabled the differentiation between HeV and NiV infections, since as expected, the sera displayed higher reactivity with the respective homologous antigens. In the future, these assays will present valuable tools for serosurveillance of swine and possibly other livestock or wildlife species in affected areas. Such studies will help assessing the potential risk for human and animal health worldwide by elucidating the distribution of henipaviruses.
    Matched MeSH terms: Leishmania/metabolism
  15. Fulltext Phlebotomine sand flies (Diptera: Psychodidae) and sand fly-borne pathogens in the Greater Mekong Subregion: a systematic review
    Hustedt J, Prasetyo DB, Fiorenzano JM, von Fricken ME, Hertz JC
    Parasit Vectors, 2022 Oct 05;15(1):355.
    PMID: 36199150 DOI: 10.1186/s13071-022-05464-8
    Phlebotomine sand flies are proven or suspected vectors of several pathogens of importance, including leishmaniasis, bartonellosis and sand fly fevers. Although sand flies have a worldwide distribution, there has been limited research published on sand flies and sand fly-borne pathogens throughout the Greater Mekong Sub-region (GMS). This review followed the PRISMA guidelines to determine the biodiversity and presence of phlebotomine sand flies and their associated pathogens in the GMS, specifically Cambodia, Thailand, the Lao People's Democratic Republic (Laos), Malaysia and Vietnam. A total of 1472 records were identified by searching electronic databases, scanning reference lists of articles and consulting experts in the field. After screening of title and abstracts, 178 records remained and were further screened for original data (n = 34), not having regional data (n = 14), duplication of data (n = 4), records not available (n = 4) and no language translation available (n = 2). A total of 120 studies were then included for full review, with 41 studies on sand fly-related disease in humans, 33 studies on sand fly-related disease in animals and 54 entomological studies focused on sand flies (5 papers contained data on > 1 category), with a majority of the overall data from Thailand. There were relatively few studies on each country, with the exception of Thailand, and the studies applied different methods to investigate sand flies and sand fly-borne diseases, impacting the ability to conduct meaningful meta-analysis. The findings suggest that leishmaniasis in humans and the presence of sand fly vectors have been reported across several GMS countries over the past 100 years, with local transmission in humans confirmed in Thailand and Vietnam. Additionally, local Mundinia species are likely transmitted by biting midges. Findings from this study provide a framework for future investigations to determine the geographic distribution and risk profiles of leishmaniasis and other associated sand fly-borne disease throughout the GMS. It is recommended that researchers expand surveillance efforts across the GMS, with an emphasis placed on entomological surveys, syndromic and asymptomatic monitoring in both humans and animals and molecular characterization of sand flies and sand fly-borne pathogens, particularly in the understudied countries of Cambodia, Vietnam and Laos.
    Matched MeSH terms: Leishmania*
  16. Fulltext Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities
    Levaique H, Pamlard O, Apel C, Bignon J, Arriola M, Kuhner R, et al.
    Molecules, 2021 Mar 11;26(6).
    PMID: 33799883 DOI: 10.3390/molecules26061551
    Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania found in tropical and sub-tropical areas, affecting 12 million people around the world. Only few treatments are available against this disease and all of them present issues of toxicity and/or resistance. In this context, the development of new antileishmanial drugs specifically directed against a therapeutic target appears to be a promising strategy. The GDP-Mannose Pyrophosphorylase (GDP-MP) has been previously shown to be an attractive therapeutic target in Leishmania. In this study, a chemical library of 5000 compounds was screened on both L. infantum (LiGDP-MP) and human (hGDP-MP) GDP-MPs. From this screening, oncostemonol D was found to be active on both GDP-MPs at the micromolar level. Ten alkyl-resorcinol derivatives, of which oncostemonols E and J (2 and 3) were described for the first time from nature, were then evaluated on both enzymes as well as on L. infantum axenic and intramacrophage amastigotes. From this evaluation, compounds 1 and 3 inhibited both GDP-MPs at the micromolar level, and compound 9 displayed a three-times lower IC50 on LiGDP-MP, at 11 µM, than on hGDP-MP. As they displayed mild activities on the parasite, these compounds need to be further pharmacomodulated in order to improve their affinity and specificity to the target as well as their antileishmanial activity.
    Matched MeSH terms: Leishmania/drug effects; Leishmania/pathogenicity; Leishmaniasis/drug therapy*
  17. Comparison of several lizard Leishmania species and strains in terms of kinetoplast minicircle and maxicircle DNA sequences, nuclear chromosomes, and membrane lipids
    Gomez-Eichelmann MC, Holz G, Beach D, Simpson AM, Simpson L
    Mol Biochem Parasitol, 1988 Jan 15;27(2-3):143-58.
    PMID: 3344003
    Eight strains of a lizard Leishmania species, L. tarentolae, were compared with four other saurian species [L. hoogstrali, L. adleri, L. agamae and Leishmania sp. LizS], with L. major from man and with Trypanosoma platydactyli, a putative lizard trypanosome, in terms of kinetoplast DNA minicircle and maxicircle sequences and in terms of nuclear chromosome patterns on orthogonal gel electrophoresis. The L. tarentolae strains fell into two major groups, one (group A) consisting of the L. tarentolae strains, UC, Krassner and Trager, derived from an Algerian gecko isolate and the other (group B) consisting of five L. tarentolae LEM strains isolated from geckos in southern France. T. platydactyli TPCL2, which was postulated by Wallbanks et al. to represent the lizard form of a French L. tarentolae strain, was closely related to the UC strain and not to the LEM strains, in all respects analyzed. Leishmania sp. LizS from a Mongolian gecko and L. hoogstrali from a Sudanese gecko showed some sequence similarities to the L. tarentolae strains, but the leishmanias said to be L. adleri from a Kenyan lacertid and L. agamae from an Israeli agamid showed no minicircle sequence similarities with lizard Leishmania and in fact were probably the same species. The maxicircle divergent region was larger in the group B strains than in the group A strains, but there were sequences in common with both groups, and not with L. hoogstrali and L. major. Four strains of L. tarentolae, the four other supposed saurian Leishmania species, three mammalian leishmanias, T. platydactyli and four other trypanosomes, T. cyclops (Malaysian macaque), T. conorrhini (Hawaiian reduviid bug), T. cruzi (man) and T. lewisi (feral rat) were analyzed for their contents of sterols and phosphoglyceride fatty acyl groups. T. platydactyli TPCL2 contained a sterol (5-dehydroepisterol), a phosphatidylcholine fatty acyl group (alpha-linolenic acid) and a phosphatidylethanolamine fatty acyl group (dihydrosterculic acid) characteristic of members of the genus Leishmania and not the genus Trypanosoma. The proportions of those lipids in the free sterol and phosphoglyceride fractions of T. platydactyli TPCL2 most closely resembled those seen in the Leishmania strains from Algerian, French, Mongolian and Sudanese geckos.
    Matched MeSH terms: Leishmania/classification; Leishmania/isolation & purification*
  18. Fulltext Capsid structure of Leishmania RNA virus 1
    Procházková M, Füzik T, Grybchuk D, Falginella F, Podešvová L, Yurchenko V, et al.
    J Virol, 2020 Nov 18.
    PMID: 33208443 DOI: 10.1128/JVI.01957-20
    Leishmania parasites cause a variety of symptoms, including mucocutaneous leishmaniasis, which results in the destruction of the mucous membranes of the nose, mouth, and throat. The species of Leishmania carrying Leishmania RNA virus 1 (LRV1), from the family Totiviridae, are more likely to cause severe disease and are less sensitive to treatment than those that do not contain the virus. Although the importance of LRV1 for the severity of leishmaniasis was discovered a long time ago, the structure of the virus remained unknown. Here, we present a cryo-electron microscopy reconstruction of the virus-like particle of LRV1 determined to a resolution of 3.65 Å. The capsid has icosahedral symmetry and is formed by 120 copies of a capsid protein assembled in asymmetric dimers. RNA genomes of viruses from the family Totiviridae are synthetized, but not capped at the 5' end, by virus RNA-polymerases. To protect viral RNAs from degradation, capsid proteins of totivirus L-A cleave the 5' caps of host mRNAs, creating decoys to overload the cellular RNA quality control system. Capsid proteins of LRV1 form positively charged clefts, which may be the cleavage sites for the 5' cap of Leishmania mRNAs. Capsid proteins of LRV1 contain a putative RNA binding site distinct from that of the related L-A virus. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative de-capping site. Such inhibitors may be developed into a treatment for mucocutaneous leishmaniasis caused by LRV1-positive species of LeishmaniaIMPORTANCE Twelve million people worldwide suffer from leishmaniasis, resulting in more than thirty thousand deaths annually. The disease has several variants that differ in their symptoms. The mucocutaneous form, which leads to disintegration of the nasal septum, lips, and palate, is predominantly caused by Leishmania parasites carrying Leishmania RNA virus 1 (LRV1). Here, we present the structure of the LRV1 capsid determined using cryo-electron microscopy. Capsid proteins of a related totivirus L-A protect viral RNAs from degradation by cleaving the 5' caps of host mRNAs. Capsid proteins of LRV1 may have the same function. We show that the LRV1 capsid contains positively charged clefts that may be sites for the cleavage of mRNAs of Leishmania cells. The structure of the LRV1 capsid enables the rational design of compounds targeting the putative mRNA cleavage site. Such inhibitors may be used as treatments for muco-cutaneous leishmaniasis.
    Matched MeSH terms: Leishmania; Leishmaniasis, Mucocutaneous; Leishmaniasis, Cutaneous; Leishmaniavirus
  19. Fulltext Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
    Akpunarlieva S, Weidt S, Lamasudin D, Naula C, Henderson D, Barrett M, et al.
    J Proteomics, 2017 02 23;155:85-98.
    PMID: 28040509 DOI: 10.1016/j.jprot.2016.12.009
    Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells. Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype.

    BIOLOGICAL SIGNIFICANCE: This paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy.

    Matched MeSH terms: Leishmania mexicana/metabolism*
  20. Ancistrobenomine a, the first naphthylisoquinoline oxygenated at Me-3, and related 5,1'-coupled alkaloids, from the "new" plant species ancistrocladusbenomensis
    Bringmann G, Dreyer M, Rischer H, Wolf K, Hadi HA, Brun R, et al.
    J Nat Prod, 2004 Dec;67(12):2058-62.
    PMID: 15620251
    Three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine A (1), 6-O-demethylancistrobenomine A (2), and 5'-O-demethylancistrocline (3), have been isolated from the stem bark of a botanically as yet undescribed highland liana Ancistrocladus sp., proposed to be named "A. benomensis" according to the region in Peninsular Malaysia where it has been discovered on the mountain of Gunung Benom. Two of the compounds possess an unprecedented structure with a novel hydroxymethylene group at C-3 of the fully dehydrogenated isoquinoline moiety. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. As typical of the so-called Ancistrocladaceae type, all of the compounds isolated bear an oxygen at C-6. Biological activities of these alkaloids against different protozoic pathogens are described.
    Matched MeSH terms: Leishmania donovani/drug effects
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