Evaluation of Beauvericin’s Activity and Mode of Action Against All Life Stages of Leishmania tropica

Abstract

Leishmaniasis is a vector-borne complex malady and causative of a broad spectrum of clinical manifestations. Leishmaniasis has elicited a global health concern, following its spread via the Leishmania parasite. L. tropica, the causative agent of cutaneous leishmaniasis, is an understudied species of Leishmania with various variables yet to be elucidated. Due to the scarce therapeutic agents available in the market, their limited efficacy, and resistance acquisition following their usage, novel interventions are imperative. Our study was executed to delineate the efficacy and resistance acquisition towards BEA by promastigotes and intracellular amastigotes of L. tropica, in association with macrophage-like cells. Moreover, RNA sequencing was employed to identify the differentially expressed genes in response to drug treatment. Our data showcased the high potency of BEA against both developmental stages of the parasite. Additionally, we conclusively demonstrated BEA’s low cytotoxicity to macrophage-like cells, with a lower value to L. tropica developmental stages. Furthermore, BEA mediated low resistance acquisition in the two distinct life stages of the parasite. In addition, RNA-Seq data revealed the overexpression of ten assembled gene sets in both life stages of the parasite following exposure to BEA. Our study elucidated an in-depth view of BEA’s potency in inhibiting the growth of L. tropica, characterized by high efficacy and low resistance acquisition to the drug. Moreover, this study showcased the various mechanisms of action of BEA through the identified differentially expressed genes within the parasite’s genome.