Abstract | BACKGROUND: METHODS: A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ). RESULTS: After doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis. CONCLUSIONS: In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.
|
Authors | Sébastien Briolant, Lionel Almeras, Maya Belghazi, Elodie Boucomont-Chapeaublanc, Nathalie Wurtz, Albin Fontaine, Samuel Granjeaud, Thierry Fusaï, Christophe Rogier, Bruno Pradines |
Journal | Malaria journal
(Malar J)
Vol. 9
Pg. 141
(May 25 2010)
ISSN: 1475-2875 [Electronic] England |
PMID | 20500856
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antimalarials
- Proteome
- Protozoan Proteins
- Doxycycline
|
Topics |
- Antimalarials
(pharmacology)
- Doxycycline
(pharmacology)
- Electrophoresis, Gel, Two-Dimensional
- Gene Expression Regulation
(drug effects)
- Genes, Protozoan
- Genomics
- Humans
- Malaria, Falciparum
(drug therapy, parasitology)
- Mitochondria
(drug effects, metabolism)
- Phenotype
- Plasmodium falciparum
(drug effects, genetics, metabolism)
- Proteome
(drug effects, genetics, metabolism)
- Proteomics
- Protozoan Proteins
(drug effects, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Schizonts
(chemistry, metabolism)
|