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Leishmania make an abundant glycoprotein and proteophosphoglycan-rich gel, called the promastigote secretory gel, in the anterior midgut of their sand fly vector. This gel is a multi-faceted virulence factor which promotes the survival and transmission of the parasites between hosts. Here, we present the case that Leishmania parasites embedded in the promastigote secretory gel should be redefined as a biofilm as it shares striking similarities in biogenesis, form, and function with biofilms of other unicellular organisms. We believe that this reinterpretation will stimulate new hypotheses and avenues of research to improve our understanding of the developmental programme of Leishmania and the interaction these parasites and other kinetoplastids have with their insect hosts.

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Indole-3-acetic acid (IAA), as an important regulator of potato growth, seriously affects the growth and yield of potato. Although many studies have reported that IAA-producing Bacillus can promote plant growth, little research has been conducted on its synthesis pathway and molecular mechanisms. In this study, an IAA-producing strain WL35 was identified as Fitibacillus barbaricus, and its yield was 48.79 mg·L-1. The results of the pot experiments showed that WL35 significantly increased plant height, stem thickness, chlorophyll content, and number of leaves of potato plants by 31.68%, 30.03%, 32.93%, and 36.59%, respectively. In addition, in the field experiments, WL35-treated plants increased commercial potato yield by 16.45%, vitamin C content by 16.35%, protein content by 75%, starch content by 6.60%, and the nitrogen, phosphorus, and potassium accumulation by 9.98%, 12.70%, and 26.76%, respectively. Meanwhile, the synthetic pathway of WL35 was found to be dominated by the tryptophan-dependent pathway, the IAM, TAM, and IPA pathways worked together, and the pathways that played a role at different times were different. Furthermore, RNA-seq analysis showed that there were a total of 2875 DEGs regulated in the samples treated with WL35 seed dressing compared with the CK, of which 1458 genes were up-regulated and 1417 genes were down-regulated. Potato roots express differential genes enriched in processes such as carbohydrate metabolism processes and cellular polysaccharide metabolism, which regulate potato plant growth and development. The above results provide a theoretical basis for the further exploration of the synthesis pathway of IAA and its growth-promoting mechanism in potato.

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Cutaneous leishmaniasis (CL) is a tropical disease endemic in many parts of the world. Characteristic clinical manifestations of CL include the formation of ulcerative skin lesions that can inflict life-long disability if left untreated. Although drugs are available, they are unaffordable and out of reach for individuals who need them the most. Developing a highly cost-efficient CL vaccine could address this problem but such a vaccine remains unavailable. Here, we developed a chimeric influenza virus-like particle expressing the Leishmania amazonensis promastigote surface antigen (LaPSA-VLP). LaPSA-VLPs were self-assembled in Spodoptera frugiperda insect cell lines using the baculovirus expression system. After characterizing the vaccines and confirming successful VLP assembly, BALB/c mice were immunized with these vaccines for efficacy assessment. Sera acquired from mice upon subcutaneous immunization with the LaPSA-VLP specifically interacted with the L. amazonensis soluble total antigens. LaPSA-VLP-immunized mice elicited significantly greater quantities of parasite-specific IgG from the spleens, popliteal lymph nodes, and footpads than unimmunized mice. LaPSA-VLP immunization also enhanced the proliferation of B cell populations in the spleens of mice and significantly lessened the CL symptoms, notably the footpad swelling and IFN-γ-mediated inflammatory response. Overall, immunizing mice with the LaPSA-VLPs prevented mice from developing severe CL symptoms, signifying their developmental potential.

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Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis.

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Leishmaniasis, a debilitating disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of a female sandfly, continues to present significant challenges despite ongoing research and collaboration in vaccine development. The intricate interaction between the parasite's life cycle stages and the host's immunological response, namely the promastigote and amastigote forms, adds complexity to vaccine design. The quest for a potent vaccine against Leishmaniasis demands a comprehensive understanding of the immune mechanisms that confer long-lasting protection, which necessitates extensive research efforts. In this pursuit, innovative approaches such as reverse vaccinology and computer-aided design offer promising avenues for unraveling the intricacies of host-pathogen interactions and identifying effective vaccine candidates. However, numerous obstacles, including limited treatment options, the need for sustained antigenic presence, and the prevalence of co-infections, particularly with HIV, impede progress. Nevertheless, through persistent research endeavours and collaborative initiatives, the goal of developing a highly efficacious vaccine against Leishmaniasis can be achieved, offering hope through the latest Omics data development with immunoinformatics approaches for effective vaccine design for the prevention of this disease.

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Introduction: Leishmaniasis comprises a complex group of diseases caused by protozoan parasites from the Leishmania genus, presenting a significant threat to human health. Infection starts by the release into the skin of metacyclic promastigote (MP) form of the parasite by an infected sand fly. Soon after their release, the MPs enter a phagocytic host cell. This study focuses on finding peptides that can inhibit MP-phagocytic host cell interaction. Methods: We used a phage display library to screen for peptides that bind to the surface of L. amazonensis (causative agent for cutaneous leishmaniasis) and L. infantum (causative agent for cutaneous and visceral leishmaniasis) MPs. Candidate peptide binding to the MP surface and inhibition of parasite-host cell interaction were tested in vitro. Peptide Inhibition of visceral leishmaniasis development was assessed in BALB/c mice. Results: The selected L. amazonensis binding peptide (La1) and the L. infantum binding peptide (Li1) inhibited 44% of parasite internalization into THP-1 macrophage-like cells in vitro. While inhibition of internalization by La1 was specific to L. amazonensis, Li1 was effective in inhibiting internalization of both parasite species. Importantly, Li1 inhibited L. infantum spleen and liver infection of BALB/c mice by 84%. Conclusion: We identified one peptide that specifically inhibits L. amazonensis MP infection of host cells and another that inhibits both, L. amazonensis and L. infantum, MP infection. Our findings suggest a promising path for the development of new treatments and prevention of leishmaniasis.

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Therapeutic research is very important in the prevention and treatment of leishmaniasis due to problems such as drug resistance, scarring and disease recurrence. The aim of this study was to determine how Leishmania major responds to the anti-leishmaniasis properties of podophyllotoxin and podophyllin. Cultured Leishmania promastigotes were exposed to different concentrations of podophyllotoxin and podophyllin for 24 and 48 h. Then, during the animal phase, Balb/c mice were experimentally injected with Leishmania promastigotes. After wounding, the effects of 0.5% podophyllotoxin and 25% podophyllin on reducing wound diameter and the number of amastigotes in the wound were evaluated. Podophyllotoxin and podophyllin were 83% and 59% lethal to Leishmania major promastigotes at the highest concentrations (200 µg/ml) and time (48 h). In the in vivo study, the mean lesion diameter at the end of treatment in the negative control group was 15.10 mm compared to 14.21 mm and 11.55 mm in the 25% podophyllin and 0.5% podophyllotoxin groups, respectively. Although both agents reduced the size of mice wounds and the number of amastigotes in the wounds, podophyllotoxin was more effective in this regard. Based on the results, podophyllotoxin and podophyllin can be used as leishmaniasis drugs after further research.

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BACKGROUND: Leishmaniasis, caused by protozoan parasites of the genus Leishmania, is a neglected tropical disease with 700,000 to 1,000,000 global new cases annually. Adverse effects associated with expense, long-term treatment and drug resistance have made conventional therapies unfavorable, encouraging the search for alternative drugs based on plant products. In this study, the effect of Calotropis procera (Asclepiadaceae) extract against viability of promastigotes and amastigotes of Leishmania major was evaluated in vitro. METHODS: The extract from the leaves of C. procera seedlings was prepared using a methanol maceration method. The colorimetric cell viability 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the growth-inhibitory effect of the extract on promastigotes. The level of reactive oxygen species (ROS) in promastigote cultures was determined after treatment with the extract using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) method and compared with untreated cultures (control). After exposure to the extract the expression levels of tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ) and inducible nitric oxide synthase (iNOS) genes were determined and compared to control in peripheral blood mononuclear cells (PBMCs) infected with L. major. RESULTS: Based on the MTT assay, the C. procera extract significantly reduced the proliferation of L. major promastigotes with IC50 values of 377.28 and 222.44 µg/mL for 24 and 72 h, respectively (p < 0.01). After treatment with 222.44 and 377.28 µg/mL of C. procera extract, ROS production in L. major promastigote cultures increased 1.2- to 1.65-fold and 2- to 4-fold compared to the control, respectively (p < 0.05). C. procera extract induced significant increases in gene expression of TNF-α (2.76-14.83 fold), IFN-γ (25.63-threefold) and iNOS (16.32-3.97 fold) in infected PBMCs compared to control (p < 0.01). CONCLUSIONS: On the basis of its anti-leishmanial activity, C. procera can be considered as a promising new plant source for the potential treatment of leishmaniasis.

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Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The aim was to chemically characterize the essential oil (EO) obtained from P. brevipedunculata (EO-PB) by hydrodistillation and a microemulsion formulated with EO (ME-PB), Tween 80 and Transcutol P, assess the leishmanicidal effect against Leishmania (L.) amazonensis promastigotes and cytotoxicity against RAW 264.7. EO-PB and ME-PB were analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Monoterpene hydrocarbons were noteworthy among the identified compounds. The main EO-PB constituents were α-pinene and limonene, followed by neral and geranial, which were maintained in ME-PB. EO-PB presented an inhibitory concentration (IC50) of 20 µg/mL and ME-PB of 0.93 µg/mL. ME-PB inhibition towards the parasite was 20-fold higher than that of EO-PB. This indicated that EO incorporation to the microemulsion resulted in optimized biological activity. Selectivity indices indicate that ME-PB is more selective concerning parasite inhibition. Thus, ME-PB may comprise an adequate approach against Leishmania, as the inhibitory concentration (IC50) promastigotes was lower than that considered toxic for cells cell cytotoxicity of 50% (CC50).

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Currently, zinc oxide (ZnO) particles are used in nanotechnology to destroy a wide range of microorganisms. Although pentavalent antimony compounds are used as antileishmanial drugs, they are associated with several limitations and side effects. Therefore, it is always desirable to try to find new and effective treatments. The aim of this research is to determine the antileishmanial effect of ZnO particles in comparison to the Antimoan Meglumine compound on promastigotes and amastigotes of Leishmania major (MRHO/IR/75/ER). After the extraction and purification of macrophages from the peritoneal cavity of C57BL/6 mice, L. major parasites were cultured in Roswell Park Memorial Institute-1640 culture medium containing fetal bovine serum (FBS) 10% and antibiotic. In this experimental study, the effect of different concentrations of nanoparticles was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric method, in comparison to the glucantime on promastigotes, amastigotes and healthy macrophages in the culture medium. The amount of light absorption of the obtained color from the regeneration of tetrazolium salt to the product color of formazan by the parasite was measured by an enzyme-linked immunosorbent assay (ELISA) reader, and the IC50 value was calculated. IC50 after 24 h of incubation was calculated as IC50 = 358.6 µg/mL. The results showed, that the efficacy of ZnO nanoparticles was favorable and dose-dependent. The concentration of 500 µg/mL of ZnO nanoparticles induced 84.67% apoptosis after 72. Also, the toxicity of nanoparticles was less than the drug. Nanoparticles exert their cytotoxic effects by inducing apoptosis. They can be suitable candidates in the pharmaceutical industry in the future.

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BACKGROUND: Cutaneous leishmaniasis is among the neglected diseases in the world. Pentavalent antimonial compounds are considered the first-line treatment for this disease. However, using alternative natural products has received great attention due to the side effects of chemical drugs and drug resistance of the Leishmania parasite. The present study aims to investigate the effect of Satureja khuzestanica essential oil (SKEO) on MDR1 gene expression. METHODS: In this study, standard strains of Leishmania major promastigotes were exposed to 5, 10, 15, and 20 µg/ml of SKEO. MDR1 gene expression of parasites exposed to essential oil was evaluated using real-time PCR. GAPDH was employed as the housekeeping gene for internal control. RESULTS: Despite the increase, no statistically significant difference was observed in the relative expression of the MDR1 gene between the control group and the groups containing 5, 10, and 20 µg/ml of SKEO (P > 0.05). The relative expression of the MDR1 gene significantly increased in the group containing 15 µg/ml of essential oil compared to the control one (P < 0.05). CONCLUSION: This study showed that the use of essential oil of Satureja khuzestanica plant can have an increasing effect on the expression of MDR1 gene of Leishmania promastigotes, which is the best case if Satureja khuzestanica essential oil reduces the expression of MDR1 gene. So it seems that the use of essential oil of Satoria plant is effective in controlling Leishmania parasite, but its concentrations induce drug resistance. As a result, concentrations of essential oil should be used that have a controlling effect on the growth and proliferation of Leishmania parasite and also have the least effect on the induction of MDR1 gene expression.

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PURPOSE: Visceral leishmaniasis (VL) is a systemic and parasitic disease that is usually fatal if left untreated. VL is endemic in different parts of Iran and is caused mainly by Leishmania infantum. This study aimed to recognition immunoreactive proteins in amastigote-like and promastigote stages of L. infantum (Iranian strain) by antibodies present in the sera of VL patients. METHODS: Total protein extract from amastigote-like and promastigote cells was separated by two-dimensional electrophoresis (2DE). To detect the immunoreactive proteins, 2DE immunoblotting method was performed using different pools of VL patients' sera. RESULTS: Approximately 390 and 430 protein spots could be separated in 2DE profiles of L. infantum amastigote-like and promastigote stages, respectively. In immunoblotting method, approximately 295 and 135 immunoreactive proteins of amastigotes-like reacted with high antibody titer serum pool and low antibody titer serum pool, respectively. Approximately 120 and 85 immunoreactive proteins of promastigote extract were recognized using the high antibody titer sera pool and low antibody titer sera, respectively. CONCLUSION: The present study has recognized a number of antigenic diversity proteins based on the molecular weight and pH in amastigote-like and promastigote stages of L. infantum. These results provide us a new concept for further analysis development in the field of diagnosis biomarkers and vaccine targets.

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Leishmaniasis is an emerging tropical infectious disease caused by a protozoan parasite of the genus Leishmania. In this work, the molecular hybridization between a trimethoxy chalcone and a sulfonamide group was used to generate a series of sulfonamide-chalcones. A series of eight sulfonamide-chalcone hybrids were made with good yields (up to 95%). These sulfonamide-chalcones were tested against promastigotes of Leishmania amazonensis and cytotoxicity against mouse macrophages, which showed good antileishmanial activity with IC50 = 1.72-3.19 µM. Three of them (10c, 10g, and 10h) were also highly active against intracellular amastigotes and had a good selectivity index (SI > 9). Thus, those three compounds were docked in the cytosolic tryparedoxin peroxidase (cTXNPx) enzyme of the parasite, and molecular dynamics simulations were carried out. This enzyme was selected as a target protein for the sulfonamide-chalcones due to the fact of the anterior report, which identified a strong and stable interaction between the chalcone NAT22 (6) and the cTXNPx. In addition, a prediction of the drug-likeness, and the pharmacokinetic profile of all compounds were made, demonstrating a good profile of those chalcones.

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Leishmaniasis, a neglected tropical disease, is caused by protozoal parasites of the genus Leishmania. Clinical manifestations vary from asymptomatic to lethal grade depending on the type of the disease. The currently available antileishmanial drugs suffer from considerable limitations. There is a dire need for better and safer drugs and/or vaccines to eradicate this disease. There are enormous developments ongoing in this field. Newer combinations of existing drugs and newer drugs targeting these intracellular parasites as well as their vectors are being tried to control the disease. Attempts to develop vaccines to enhance the immunity of the patient have shown some promise. This article is a peep into the recent patent developments in this field.

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Background: Currently, there is no safe and effective vaccine against leishmaniasis and existing therapies are inadequate due to high toxicity, cost and decreased efficacy caused by the emergence of resistant parasite strains. Some indazole derivatives have shown in vitro and in vivo activity against Trichomonas vaginalis and Trypanosoma cruzi. On that basis, 20 indazole derivatives were tested in vitro against Leishmania amazonensis. Objective: To evaluate the in vitro activity of twenty 2-benzyl-5-nitroindazolin-3-one derivatives against L. amazonensis. Design: For the selection of promising compounds, it is necessary to evaluate the indicators for in vitro activity. For this aim, a battery of studies for antileishmanial activity and cytotoxicity were implemented. These results enabled the determination of the substituents in the indazole derivatives responsible for activity and selectivity, through the analysis of the structure-activity relationship (SAR). Methods: In vitro cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for 20 compounds. Compounds that showed adequate selectivity were tested against intracellular amastigotes. The SAR from the results in promastigotes was represented using the SARANEA software. Results: Eight compounds showed selectivity index >10% and 50% inhibitory concentration <1 µM against the promastigote stage. Against intracellular amastigotes, four were as active as Amphotericin B. The best results were obtained for 2-(benzyl-2,3-dihydro-5-nitro-3-oxoindazol-1-yl) ethyl acetate, with 50% inhibitory concentration of 0.46 ± 0.01 µM against amastigotes and a selectivity index of 875. The SAR study showed the positive effect on the selectivity of the hydrophilic fragments substituted in position 1 of 2-benzyl-5- nitroindazolin-3-one, which played a key role in improving the selectivity profile of this series of compounds. Conclusion: 2-bencyl-5-nitroindazolin-3-one derivatives showed selective and potent in vitro activity, supporting further investigations on this family of compounds as potential antileishmanial hits.

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Cutaneous and visceral leishmaniasis are public health problems in Africa, Asia, Europe, and America. The treatment has a high cost and toxicity. Thus, this work aims to evaluate the leishmanicidal activity of alpha-bisabolol and its three synthetic derivatives, P1, P2, and P3, on the promastigotes and amastigotes Leishmania infantum and L. amazonensis forms. Alpha-bisabolol showed the lowest IC50 with 3.43 for L. amazonensis promastigotes, while P1 was the most toxic for L. infantum with an IC50 of 9.10. The derivative P3 was better for the amastigote form, with an IC50 of 3.39 for L. amazonensis. All the compounds effectively decreased the intracellular load of amastigote and its ability to turn promastigote again. Thus, alpha-bisabolol and its three synthetic derivatives were effective in their leishmanicidal activity. Therefore, it can be an option for developing new treatments against leishmaniasis.

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To date, Leishmania spp. vaccine studies have mainly focused on cellular immunity induction, which plays a crucial role in host protection. In contrast, vaccine-induced humoral immunity is largely neglected. Virus-like particle (VLP) vaccines generated using the baculovirus expression system are well-known inducers of humoral immunity and would serve as a suitable platform for evaluating humoral immunity-mediated protection against visceral Leishmaniasis. In this study, we investigated the humoral immunity evoked through VLPs expressing the L. donovani promastigote surface antigen (PSA-VLPs) and assessed their contribution to protection in mice. PSA-VLPs vaccines were generated using the baculovirus expression system and used for mouse immunizations. Mice were intramuscularly immunized twice with PSA-VLPs and challenged with L. donovani to confirm vaccine-induced protective immunity. PSA-VLP immunization elicited parasite-specific antibody responses in the sera of mice, which were induced in a dose-dependent manner. B cell, germinal center B cell, and memory B cell responses in the spleen were found to be higher in vaccinated mice compared to unimmunized controls. PSA-VLP immunization diminished the production of pro-inflammatory cytokines IFN-γ and IL-6 in the liver. Overall, the PSA-VLPs conferred protection against L. donovani challenge infection by reducing the total parasite burden within the internal organs. These results suggest that PSA-VLPs induced protective immunity against the L. donovani challenge infection.

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Leishmaniasis is caused by ∼20 species of Leishmania that affects millions in endemic areas. Available therapies are not sufficient to effectively control the disease, cause severe side effects and eventually lead to drug resistance, making the discovery of novel therapeutic molecules an immediate need. Molecular target-based drug discovery, where the target is a defined molecular gene, protein or a mechanism, is a rationale driven approach for novel therapeutics. Humans obtain the essential amino acid such as threonine from dietary sources, while Leishmania synthesize it de-novo. Enzymes of the threonine biosynthesis pathway, including the rate limiting Homoserine kinase (HSK) which converts L-homoserine into ortho-phospho homoserine are thus attractive targets for rationale driven therapy. The absence of HSK in humans and its presence in Leishmania donovani enhances the opportunity to exploit HSK as a molecular target for anti-leishmanials therapeutic development. In this study, we utilize structure-based high throughput drug discovery (SBDD), followed by biochemical validation and identified two potential inhibitors (RH00038 and S02587) from Maybridge chemical library that targets L. donovani HSK. These two inhibitors effectively induced the mortality of Leishmania donovani in both amastigote and promastigote stages, with one of them being specific to parasite and twice as effective as the standard therapeutic molecule.

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Leishmaniasis is an infectious disease caused by protozoan species in the genera Leishmania and Endotrypanum. Current antileishmanial drugs are limited due to adverse effects, variable efficacy, the development of resistant parasites, high cost, parenteral administration and lack of availability in endemic areas. Therefore, active searching for new antileishmanial drugs has been done for years, mainly by academia. Drug screening techniques have been a challenge since the intracellular localization of Leishmania amastigotes implies that the host cell may interfere with the quantification of the parasites and the final estimation of the effect. One of the procedures to avoid host cell interference is based on its detergent-mediated lysis and subsequent transformation of viable amastigotes into promastigotes, their proliferation and eventual quantification as an axenic culture of promastigotes. However, the use of detergent involves additional handling of cultures and variability. In the present work, cultures of intracellular amastigotes were incubated for 72 h at 26 °C after exposure to the test compounds and the transformation and proliferation of parasites took place without need of adding any detergent. The assay demonstrated clear differentiation of negative and positive controls (average Z´ = 0.75) and 50% inhibitory concentrations of compounds tested by this method and by the gold standard enumeration of Giemsa-stained cultures were similar (p = 0.5002) and highly correlated (r = 0.9707). This simplified procedure is less labor intensive, the probability of contamination and the experimental error are reduced, and it is appropriate for the automated high throughput screening of compounds.

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Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of Leishmania spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid phosphatase (ScAP), are also ligands. CRP binding was mainly associated with the flagellar pocket when LPG deficient Leishmania mexicana parasites were examined by fluorescent microscopy, consistent with binding to secreted material. ScAP is a major ligand in purified fPPG from parasite culture as demonstrated by much reduced binding to a ScAP deficient mutant fPPG in plate binding assays and ligand blotting. Nevertheless, in sandfly derived PSG fPPG is a major component and the major CRP binding component. Previously we showed high avidity of CRP for LPG ligand required multiple disaccharide repeats. ScAP and fPPG only have short repeats but they retain high avidity for CRP revealed by surface plasmon resonance because they are found in multiple copies on the phosphoglycan. The fPPG from many species such as L. donovani and L. mexicana bound CRP strongly but L. tropica and L. amazonensis had low amounts of binding. The extent of side chain substitution of [-PO4-6Galß1-4Manα1-] disaccharides correlates inversely with binding of CRP. The ligand for the CRP on different species all had similar binding avidity as the half maximal binding concentration was similar. Since the PSG is injected with the parasites into host blood pools and phosphoglycans (PG) are known to deplete complement, we showed that CRP makes a significant contribution to the activation of complement by PSG using serum from naive donors.

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