Global distribution of treatment resistance gene markers for leishmaniasis.

BACKGROUND: Pentavalent antimonials (Sb(V)) such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) are used as first-line treatments for leishmaniasis, either alone or in combination with second-line drugs such as amphotericin B (Amp B), miltefosine (MIL), methotrexate (MTX), or cryotherapy. Therapeutic aspects of these drugs are now challenged because of clinical resistance worldwide. METHODS: We reviewedthe recent original studies were assessed by searching in electronic databases such as Scopus, Pubmed, Embase, and Web of Science. RESULTS: Studies on molecular biomarkers involved in drug resistance are essential for monitoring the disease. We reviewed genes and mechanisms of resistance to leishmaniasis, and the geographical distribution of these biomarkers in each country has also been thoroughly investigated. CONCLUSION: Due to the emergence of resistant genes mainly in anthroponotic Leishmania species such as L. donovani and L. tropica, as the causative agents of ACL and AVL, respectively, selection of an appropriate treatment modality is essential. Physicians should be aware of the presence of such resistance for the selection of proper treatment modalities in endemic countries.

Antiproliferative properties of Turmerone on Leishmania major: Modes of action confirmed by antioxidative and immunomodulatory roles.

Treatment of leishmaniasis by conventional synthetic compounds has faced a serious challenge worldwide. This study was performed to evaluate the effect and modes of action of aromatic Turmerone on the Leishmania major intra-macrophage amastigotes, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. In the findings, the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Turmerone plus meglumine antimoniate (Glucantime®; MA) than MA alone, especially at 50 µg/mL. In addition, Turmerone demonstrated no cytotoxicity as the selectivity index (SI) was 21.1; while it induced significant apoptosis in a dose-dependent manner on L. major promastigotes. In silico molecular docking analyses indicated an affinity of Turmerone to IL-12, with the MolDock score of - 96.8 kcal/mol; which may explain the increased levels of Th1 cytokines and decreased level of IL-10. The main mechanism of action is more likely associated with stimulating a powerful antioxidant and promoting the immunomodulatory roles in the killing of the target organism.

Plant-mediated green synthesis of silver nanoparticles using Trifolium resupinatum seed exudate and their antifungal efficacy on Neofusicoccum parvum and Rhizoctonia solani.

In recent years, biosynthesis and the utilisation of silver nanoparticles (AgNPs) has become an interesting subject. In this study, the authors investigated the biosynthesis of AgNPs using Trifolium resupinatum (Persian clover) seed exudates. The characterisation of AgNPs were analysed using ultraviolet-visible spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infra-red spectroscopy. Also, antifungal efficacy of biogenic AgNPs against two important plant-pathogenic fungi (Rhizoctonia solani and Neofusicoccum Parvum) in vitro condition was evaluated. The XRD analysis showed that the AgNPs are crystalline in nature and have face-centred cubic geometry. TEM images revealed the spherical shape of the AgNPs with an average size of 17 nm. The synthesised AgNPs were formed at room temperature and kept stable for 4 months. The maximum distributions of the synthesised AgNPs were seen to range in size from 5 to 10 nm. The highest inhibition effect was observed against R. solani at 40 ppm concentration of AgNPs (94.1%) followed by N. parvum (84%). The results showed that the antifungal activity of AgNPs was dependent on the amounts of AgNPs. In conclusion, the AgNPs obtained from T. resupinatum seed exudate exhibit good antifungal activity against the pathogenic fungi R. solani and N. Parvum.

The role of GlcNAc-PI-de-N-acetylase gene by gene knockout through homologous recombination and its consequences on survival, growth and infectivity of Leishmania major in in vitro and in vivo conditions.

At present, there are no efficacious vaccines or effective drugs against leishmaniasis; therefore new and innovative control methods are urgently required. One way to achieve this important goal is through using reverse genetic engineering to evaluate important enzymes, proteins and macromolecules. One of the most important enzymes for Glycosylphosphatidylinositol (GPI) biosynthetic pathways is GlcNAc-PI-de-N-acetylase (GPI12). The molecular constructs were cloned in Escherichia coli strain Top 10 and confirmed by molecular methods and were transfected by electroporation into Leishmania major. We demonstrated that two alleles of the GPI12 gene in L. major were successfully removed and enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. We were able to produce a mutant parasite that caused no damaged to the host. Further investigations are essential to check the safety profile in laboratory animals.