HAS 1: A natural product from soil-isolated Streptomyces species with potent activity against cutaneous leishmaniasis caused by Leishmania tropica
Abstract
Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World
Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war
and the significant displacement of refugees aggravated the spread of this ailment into
several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria,
Leishmania tropica is identified as one of the most aggressive and endemic identified
species, causing localized or generalized lesions, often chronic or relapsing.
Pentavalent antimonial drugs are currently used as first line treatment against CL.
Nonetheless, these drugs exhibit several limitations, including the repetitive painful
injections, high cost, poor availability, and mainly systemic toxicity. Besides, the
emergence of acquired parasitic resistance hinders their potency, stressing the
need for new therapies to combat CL. Natural products (NPs) epitomize a
valuable source in drug discovery. NPs are secondary metabolites (SMs) produced
by plants, sponges, or a wide variety of organisms, including environmental
microorganisms. The EMR is characterized by its immense biodiversity, yet it
remains a relatively untapped area in drug discovery. NPs of the region were
explored over the last 2 decades, but their discoveries lack biogeographical
diversity and are limited to the Red Sea. Here, we isolated previously uncultured
environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in
southeast Lebanon. When fermented in one of our production media named INA,
HAS1 produced a crude extract with significant potency against a clinical Leishmania
tropica isolate. Using bio-guided fractionation, the bioactive compound was purified
and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as
strong candidates for treating Leishmania tropica and further dwells on the
importance of these natural sources to combat microbial infections
Journal/Conference Information
Frontiers in Pharmacology ,DOI: 13:1023114.
doi: 10.3389/fphar.2022.1023114, Volume: 10.3389/fphar.2022.1023114, Issue: 10.3389/fphar.2022.1023114, Pages Range: 01-14,