Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions
Issued Date
2024-12-01
Resource Type
eISSN
19352735
Scopus ID
2-s2.0-85214320470
Pubmed ID
39689148
Journal Title
PLoS neglected tropical diseases
Volume
18
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS neglected tropical diseases Vol.18 No.12 (2024) , e0012716
Suggested Citation
Anuntasomboon P., Siripattanapipong S., Unajak S., Choowongkomon K., Burchmore R., Leelayoova S., Mungthin M., E-Kobon T. Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions. PLoS neglected tropical diseases Vol.18 No.12 (2024) , e0012716. doi:10.1371/journal.pntd.0012716 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102687
Title
Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions
Corresponding Author(s)
Other Contributor(s)
Abstract
Amphotericin B (AmB) is a potent antifungal and antiparasitic medication that exerts its action by disrupting the cell membrane of the leishmanial parasite, leading to its death. Understanding the genetic alterations induced by Amphotericin B is crucial for gaining insights into drug resistance mechanisms and developing more effective treatments against Leishmania infections. As a new Leishmania species, the molecular response of Leishmania orientalis to anti-leishmanial drugs has not been fully explored. In this study, Leishmania orientalis strain PCM2 culture was subjected to AmB exposure at a concentration of 0.03 uM over 72 hours compared to the control. The genomic alteration and transcriptomic changes were investigated by utilising the whole genome and RNA sequencing methods, followed by the analysis of single nucleotide polymorphisms (SNPs), differential gene expression, and chromosomal copy number variations (CNVs) assessed using read depth coverage (RDC) values across the entire genome. The chromosomal CNV analysis showed no significant difference between L. orientalis from the control and AmB-treated groups. The distribution of SNPs displayed notable variability, with higher SNP incidence in the control group compared to the AmB-treated group. Gene ontology analysis unveiled functions of the SNPs -associated genes involved in transporter function, genetic precursor synthesis, and purine nucleotide metabolism. Notably, the impact of AmB treatment on the L. orientalis gene expression profiles exhibited diverse expressional alterations, particularly the downregulation of pivotal genes such as the tubulin alpha chain gene. The intricate interplay between SNPs and gene expression alterations might underscore the complex regulatory networks underlying the AmB resistance of L. orientalis strain PCM2.