Biology subjects

Omelianczyk, R. I.

Publications and source records attributed to Omelianczyk, R. I..

3 recordsLinked to original sources

bioRxiv2025

Sickle cell status skews malaria parasite genotype at infection

Sickle cell hemoglobin (HbS) confers protection against symptomatic malaria caused by Plasmodium falciparum. HbS carriers with symptomatic malaria harbour parasites enriched for sickle-associated alleles (Pfsa+), which appear to partially overcome HbS-mediated protection, but their role in asymptomatic infections is unclear. Here, we conducted a cross-sectional survey of 2,246 healthy school children in a region of high malaria transmission region in Cameroon. Analysing parasite Pfsa and human HbS genotypes for 1,701 asymptomatic P. falciparum infections confirmed that heterozygous HbS (HbAS) and homozygous non-HbS (HbAA) genotypes have similar rates of asymptomatic infection. However, the HbS genotype is strongly associated with parasites carrying Pfsa+ alleles at Pfsa1 and Pfsa3 loci, indicating a selective advantage for these alleles in HbS carriers. Our findings reveal that the protective effect of HbS is complex, where HbS has a protective effect prior to symptoms against Pfsa- parasites and Pfsa+ alleles may contribute to lower rates of symptomatic disease in HbS carriers. HbS protection against malarial disease should consider both resistance and tolerance and ongoing co-evolution with parasites.

genetics↗

bioRxiv2025

Epitranscriptomic Dysregulation Underpins Artemisinin Mechanism of Action

Artemisinin has long been a first-line antimalarial. Yet, its mode of action is still poorly understood. Emergence of artemisinin-resistant strains highlight the importance of addressing this question so as to develop better drugs and overcome resistance. In this study, we performed RNA-sequencing and proteomics studies on artemisinin treated parasites indicated a striking difference in the codon-usage pattern of differentially translated genes. Using a liquid chromatography-coupled mass spectrometry (LC-MS)-based platform, we have quantified the full spectrum of modified ribonucleosides on tRNA in P. falciparum in response to the drug. We found that N6-threonyl-carbomyladenosine (t6A), a universal tRNA modification found at position 37 is hypomodified in response to artemisinin induced stress. Additionally, we also found that artemisinin treatment resulted in a downregulation of PfSua5, an enzyme involved in the t6A biosynthesis machinery. These findings provide new insights into how artemisinin works. More broadly, the findings exposes the tRNA epitranscriptome as a vulnerability in the parasite that can be exploited for new drugs.

microbiology↗

bioRxiv2020

Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo

Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth. We show that upregulation of the specific PfEMP1, VAR2CSA and the RIFIN PF3D7_1254800 provides the parasite with protection from macrophage phagocytosis and natural killer cell mediated killing. Taken together, these findings reveal new insights on the molecular and cellular mechanisms that coordinate the immune escape process the parasite utilizes in vivo. As immune evasion may be particularly important during the establishment of the blood stage infection when parasite numbers are still relatively small, identification of specific parasite variant surface antigens provides targets for developing more effective vaccines by targeting parasite immune evasion.

microbiology↗