| 1. |
- Chan, S, et al.
(författare)
-
Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
- 2017
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 723-
-
Tidskriftsartikel (refereegranskat)abstract
- Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.
|
|
| 2. |
- Ch'ng, JH, et al.
(författare)
-
Enhanced virulence of Plasmodium falciparum in blood of diabetic patients
- 2021
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6, s. e0249666-
-
Tidskriftsartikel (refereegranskat)abstract
- Rising prevalence of diabetes in sub-Saharan Africa, coupled with continued malaria transmission, has resulted more patients dealing with both communicable and non-communicable diseases. We previously reported that travelers with type 2 diabetes mellitus (T2DM) infected with Plasmodium falciparum were three times more likely to develop severe malaria than non-diabetics. Here we explore the biological basis for this by testing blood from uninfected subjects with type 1 and type 2 diabetes, ex vivo, for their effects on parasite growth and rosetting (binding of infected erythrocytes to uninfected erythrocytes). Rosetting was associated with type 2 diabetes, blood glucose and erythrocyte sedimentation rate (ESR), while parasite growth was positively associated with blood glucose, glycated hemoglobin (HbA1c), body mass index (BMI), fibrinogen and triglycerides. This study establishes a link between diabetes and malaria virulence assays, potentially explaining the protective effect of good glycemic control against severe malaria in subjects with diabetes.
|
|
| 3. |
|
|
| 4. |
- Ch'ng, JH, et al.
(författare)
-
Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications
- 2016
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 29317-
-
Tidskriftsartikel (refereegranskat)abstract
- The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds. A pilot screen of 2693 compounds identified Malaria Box compound MMV006764 as a potential candidate. Although it reduced rosetting by a modest 20%, MMV006764 was validated to be similarly effective against both blood group O and A rosettes of three laboratory parasite lines. Coupled with its antiplasmodial activity and drug-likeness, MMV006764 represents the first small-molecule compound that disrupts rosetting and could potentially be used in a resource-limited setting to treat patients deteriorating rapidly from malaria complications. Such dual-action drugs that simultaneously restore microcirculation and reduce parasite load could significantly reduce malaria morbidity and mortality.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
