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Updated: Mar 12, 2026
Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Plasmodium falciparum GTP-cyclohydrolase 1 (Pfgch1) Gene Copy Number Variation and Its Implications in antimalarial
Aparajita Sen1,2, Priyanka Sharma1,3, Supriya Sharma1
1ICMR-National Institute of Malaria Research, Sector-8, Dwarka, New Delhi, India.
Background Objectives:
Drug-resistant strains of Plasmodium falciparum pose a major challenge to malaria control and elimination. The present study focuses on the GTP-cyclohydrolase 1 (Pfgch1) gene, a key enzyme in the folate biosynthesis pathway, known to play a role in antimalarial (Sulfadoxine-Pyrimethamine, commonly used in combination therapies) resistance. An increase in Pfgch1 copy number is hypothesized to compensate for the mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes associated with Sulfadoxine-Pyrimethamine resistance.
Methods:
We analyzed Pfgch1 gene copy number variation (CNV) in one hundred one P. falciparum isolates collected from Northeast India, using quantitative PCR and the findings of the CNV were used to determine the association with drug resistance genes Pfdhfr and Pfdhps.
Results:
The analysis revealed a significant variation in the Pfgch1 gene copy number among the isolates, with most isolates carrying a single copy. Notably, higher copy numbers were significantly associated with the presence of mutations in the Pfdhfr and Pfdhps genes.
Interpretation Conclusion:
A statistically significant positive correlation was observed between mutations in the Pfdhfr and Pfdhps genes and increased CNVs in the Pfgch1 gene. Further investigation is needed to elucidate the correlation between Pfgch1 amplification and how Pfdhfr/Pfdhps mutations contribute to antimalarial drug resistance in P. falciparum. This research finding may help to detect and mitigate the spread of antifolate-resistant P. falciparum.
