Aspergillus spp. metabolitlerinin Leishmania spp. patogenez yolakları üzerindeki etkilerinin Amphotericin B ile karşılaştırmalı moleküler analizi: İlaç geliştirmeye yönelik in vitro çalışmalar


Kurt Ö., Bayram Akçapinar G.

Türkiye Sağlık Enstitüleri Başkanlığı (TÜSEB) Araştırma Projesi, 2023 - 2024

  • Proje Türü: Türkiye Sağlık Enstitüleri Başkanlığı (TÜSEB) Araştırma Projesi
  • Başlama Tarihi: Mayıs 2023
  • Bitiş Tarihi: Mayıs 2024

Proje Özeti

Leishmaniasis is a protozoal infection caused by 25 different Leishmania species and transmitted by Phlebotomus spp. arthropods.

This infection is seen 98 countries in the world, especially in developing subtropical countries, and could cause more than a million

cases worldwide every year. Visceral leishmaniasis (VL), known also as Kala-Azar, is the highly lethal clinical manifestation of

leishmaniasis. The causative agent of VL in Turkey is Leishmania infantum, which is common in Mediterranean Basin. Mortality is

more than 95% in VL cases unless treated. The primary choice of treatment has long been pentavalent antimonials in VL.

Amphotericin B, which is not preferred in VL treatment for its high costs in developing countries could also be used. Drug resistance

and side effects of anti-leishmanial agents are common problems and new drug trials are assessed in many countries. Research on

natural products is mostly primary in this context. Regarding the rich biodiversity of plants and fungi in our country, it is estimated

that many natural anti-parasitic agents could be present. The aim of this study is the molecular comparison of the metabolites of

Aspergillus species, the fungi that is common and easily achieved in nature with documented anti-microbial efficacies with

amphotericin B on Leishmania infantum, in vitro. Initially, the metabolite diversity of Aspergillus sp. will be enriched by cultivation in

different media. Then, metabolites of Aspergillus spp, which were purified by ultracentrifugation and lyophilized, will be exposed to

L. infantum isolates propagated in RPMI-1640 medium in pre-determined conditions and in comparison, with Amphotericin B, and

their effects on the viability will be assessed via XTT testing. Thus, effective metabolites with EC50 levels will be determined,

followed by the comparison with amphotericin B on gene expression assessments over predetermined pathways with effects on

pathogenesis, in vitro. Among the culture-drug mixtures with detected EC50 levels will be assessed, RNA will be obtained, converted

to cDNA to obtain products for real time PCR. In the following phase of the project, the molecule(s) that are thought to be effective

against L. infantum will be assessed over advanced in vivo and in silico studies.