Recent advances and new strategies in Leishmaniasis diagnosis

Brito, Rory Cristiane Fortes de; Aguiar-Soares, Rodrigo Dian de Oliveira; Cardoso, Jamille Mirelle de Oliveira; Coura‐Vital, Wendel; Roatt, Bruno Mendes; Reis, Alexandre Barbosa

doi:10.1007/s00253-020-10846-y

Cited by 39 publications

(27 citation statements)

References 89 publications

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“…Leishmaniasis is caused by approximately 20 protozoan parasite species of the genus Leishmania , which are transmitted to humans by more than 30 different species of phlebotomine sandflies [ 4 ]. The distinct species of Leishmania cause at least four separate syndromes: visceral leishmaniasis (VL, also known as kala-azar), post-kala-azar dermal leishmaniasis (PKDL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

et al. 2021

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The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

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Section: Introductionmentioning

confidence: 99%

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

et al. 2021

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“…The detection of leishmaniasis in bone marrow or other biological specimens is the gold standard for the diagnosis of VL, and is highly specific. However, the amount of parasites in the sample and the experience of pathologists can affect sensitivity[ 10 - 12 ]. Serum immunological detection aimed at rK39 IgG antibody detection can detect anti-leishmaniasis antibody in human serum.…”

Section: Discussionmentioning

confidence: 99%

“…Serum immunological detection aimed at rK39 IgG antibody detection can detect anti-leishmaniasis antibody in human serum. It is a routinely used method to detect VL, but the antibody level does not reflect the parasite load and can remain positive for months or years, precluding its utility as a basis for evaluation of the curative effect; moreover, it is often difficult to carry out this test in non-endemic areas because of a lack of rK39 test strips[ 10 , 11 ]. Molecular biological detection includes polymerase chain reaction (PCR) methodology, which has high sensitivity and can be used to evaluate parasite load, so it can be used as a means of diagnosis and evaluation of curative effect.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing technology for diagnosis and efficacy evaluation of a patient with visceral leishmaniasis: A case report

Lin¹,

Sun²,

Wang³

et al. 2021

WJCC

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BACKGROUND Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania and transmitted by infected sand flies. VL has a low incidence in China, and its clinical presentation is complex and atypical. This disease is easily misdiagnosed and can become life-threatening within a short period of time. Therefore, early, rapid and accurate diagnosis and treatment of the disease are essential. CASE SUMMARY A 25-year-old male patient presented with the clinical manifestations of irregular fever, hepatosplenomegaly, increased polyclonal globulin, and pancytopenia. The first bone marrow puncture biopsy did not provide a clear diagnosis. In order to relieve the pressure and discomfort of the organs caused by the enlarged spleen and to confirm the diagnosis, splenectomy was performed, and hemophagocytic syndrome was diagnosed by pathological examination of the spleen biopsy. Following bone marrow and spleen pathological re-diagnosis and metagenomic next-generation sequencing (mNGS) technology detection, the patient was finally diagnosed with VL. After treatment with liposomal amphotericin B, the body temperature quickly returned to normal and the hemocytes recovered gradually. Post-treatment re-examination of the bone marrow puncture and mNGS data showed that Leishmania was not detected. CONCLUSION As a fast and accurate detection method, mNGS can diagnose and evaluate the efficacy of treatment in suspicious cases of leishmaniasis.

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“…LPGs are virulence factors constituted by 4 distinct domains: a lipid anchor, a core heptasaccharide, a polymeric repetitive tail and a cap. The core heptasaccharide is of particular interest for two reasons: it constitutes a retained feature among Leishmania species and it contains a galactofuranose ( Figure 1 ), a rare carbohydrate unit that is xenobiotic to mammals [ 3 ], conferring a keen relevance to this moiety for diagnosis and treatment development [ 4 ]. The core heptasaccharide was already been obtained by chemical synthesis, but this was a very long and difficult multistep process, with a large number of protection and deprotection steps inherent to oligosaccharide synthesis.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the Activity and Regioselectivity of a Glycosidase: Development of a Convenient Tool for the Synthesis of Specific Disaccharides

et al. 2021

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The synthesis of disaccharides, particularly those containing hexofuranoside rings, requires a large number of steps by classical chemical means. The use of glycosidases can be an alternative to limit the number of steps, as they catalyze the formation of controlled glycosidic bonds starting from simple and easy to access building blocks; the main drawbacks are the yields, due to the balance between the hydrolysis and transglycosylation of these enzymes, and the enzyme-dependent regioselectivity. To improve the yield of the synthesis of β-d-galactofuranosyl-(1→X)-d-mannopyranosides catalyzed by an arabinofuranosidase, in this study we developed a strategy to mutate, then screen the catalyst, followed by a tailored molecular modeling methodology to rationalize the effects of the identified mutations. Two mutants with a 2.3 to 3.8-fold increase in transglycosylation yield were obtained, and in addition their accumulated regioisomer kinetic profiles were very different from the wild-type enzyme. Those differences were studied in silico by docking and molecular dynamics, and the methodology revealed a good predictive quality in regards with the regioisomer profiles, which is in good agreement with the experimental transglycosylation kinetics. So, by engineering CtAraf51, new biocatalysts were enabled to obtain the attractive central motif from the Leishmania lipophosphoglycan core with a higher yield and regioselectivity.

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Recent advances and new strategies in Leishmaniasis diagnosis

Cited by 39 publications

References 89 publications

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

Next-generation sequencing technology for diagnosis and efficacy evaluation of a patient with visceral leishmaniasis: A case report

Modulation of the Activity and Regioselectivity of a Glycosidase: Development of a Convenient Tool for the Synthesis of Specific Disaccharides

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