Project description:The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used to track Coartem®efficacy are urgently needed. Often, stable resistance arises from initial, unstable phenotypes that can be identified in vitro. Here we have used the Plasmodium falciparum multidrug resistant reference strain V1S to induce LMR in vitro by culturing the parasite under continuous drug pressure for 16 months. The initial IC50 (inhibitory concentration that kills 50% of the parasite population) was 24 nM. The resulting resistant strain V1SLM, obtained after culture for an estimated 166 cycles under LM pressure, grew steadily in 378 nM of LM; this corresponds to 15 times the IC50 of the parental strain. However, after two weeks of culturing V1SLM in drug-free medium, the IC50 returned to that of the initial, parental strain V1S. This transient drug tolerance was associated with major changes in gene expression profiles: when we explored V1SLM using the PFSANGER Affymetrix custom array, we identified 184 differentially expressed (DE) genes; amongst those 18 putative transporters including the multidrug resistance gene (pfmdr1), the multidrug resistance associated protein (pfmrp1) and the V-type H+ pumping pyrophosphatase 2 (pfvp2). Moreover, our results showed significant enrichment of genes associated with fatty acid metabolism and a clear selective advantage for two genomic loci in parasites grown under LM drug pressure, suggesting these genes may contribute to LM response in P. falciparum and could prove useful as molecular markers to monitor LM susceptibility.

2011-04-01 | E-TABM-1101 | biostudies-arrayexpress

Leishmania donovani Ld 39 strain:Ld 39

Project description:Leishmania donovani Ld 39 strain:Ld 39 Genome sequencing and assembly

| PRJNA176885 | ENA

Porphyrobacter sp. LM 6 strain:LM 6

Project description:Porphyrobacter sp. LM 6 strain:LM 6 Genome sequencing and assembly

| PRJNA340879 | ENA

Streptomyces sp. SS strain:SS

Project description:Streptomyces sp. SS strain:SS Genome sequencing and assembly

| PRJNA159633 | ENA

Mitochondrial protein interaction landscape of SS-31

Project description:SS-31 is a synthetic peptide that improves mitochondrial function and is currently undergoing clinical trials for treatments of heart failure, primary mitochondrial myopathy, and other mitochondrial diseases. SS-31 interacts with cardiolipin which is abundant in the inner mitochondrial membrane, but mechanistic details of its pharmacological effects are unknown. Here we apply a chemical cross-linking/mass spectrometry method to provide direct evidence for specific interactions between SS-31 and mitochondrial proteins. The identified SS-31 interactors are functional components in ATP production and 2-oxoglutarate metabolism and signaling, consistent with improved mitochondrial function resultant from SS-31 treatment. These results offer a glimpse of the protein interaction landscape of SS-31 and provide mechanistic insight relevant to SS-31 mitochondrial therapy

2020-06-12 | PXD019484 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data