Presentation description

The evolutionary relationship between Plasmodium falciparum, the most lethal Malaria parasite affecting humans, and its human hosts continues to influence disease outcomes in endemic regions. The Sickle cell allele (HbS), resulting from a single point mutation in the beta subunit of hemoglobin, provides protection against malaria when present in heterozygous and homozygous carriers.
Recent studies have revealed a concerning development in which genetic variants in four parasite genes are strongly associated with disease severity specifically in HbS carriers. These variants significantly reduce the protection of the HbS allele, potentially jeopardizing populations where HbS prevalence is high, such as Sub-Saharan Africa. To clarify how these mutations enable parasite survival in individuals with the HbS allele, we used quantitative PCR (qPCR) to analyze gene expression in two parasite cell lines: one harboring these mutations, and one without. We analyzed these cell lines under the conditions of Sickle blood and normal blood for comparison.
Our findings revealed an upregulation in the expression of three out of four genes in the parasite strain harboring these variants compared to wildtype parasites. In the mutated sample, this upregulation occurred specifically in the three mutated parasite genes during growth in Sickle blood. This indicates that the parasite is able to recognize this Sickle blood, infect these individuals, and cause these symptoms of Malaria.
In summary, our study highlights Plasmodium falciparum's ability to bypass the protectiveness of this HbS allele. This stresses the need for genomic research to combat the evolving threat of Malaria in these endemic regions.