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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases

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The many paths to artemisinin resistance in Plasmodium falciparum

Kushankur Pandit1, Namita Surolia2, Souvik Bhattacharjee3

  • 1Department of Biology, Indian Institute of Science Education and Research, Pune, India.

Trends in Parasitology
|October 13, 2023
PubMed

Insights

Artemisinin resistance in malaria parasites is complex, involving multiple molecular pathways beyond the known PfKelch13 marker. Understanding these diverse mechanisms is crucial for developing new malaria control strategies.

Area of Science:

  • Malariology
  • Parasitology
  • Molecular Biology

Background:

  • Emerging artemisinin (ART) resistance in malaria parasites presents a significant global health challenge.
  • Mutations in PfKelch13 are key markers for ART resistance, affecting parasite processes like hemoglobin uptake and cellular stress responses.

Purpose of the Study:

  • To review the molecular, transcriptional, and metabolic pathways linked to artemisinin resistance.
  • To explore the complexity of ART resistance, including PfKelch13-independent mechanisms.

Main Methods:

  • Literature review of studies on artemisinin resistance mechanisms.
  • Analysis of molecular, cellular, and genetic data related to parasite resistance.

Main Results:

  • PfKelch13 mutations are associated with reduced hemoglobin endocytosis, unfolded protein response (UPR), elevated PI3P, and stimulated autophagy.
  • PfKelch13-independent resistance pathways exist, involving significant parasite metabolome and transcriptome reconfigurations.
  • Artemisinin resistance is multifactorial, suggesting no single universal identifier.

Conclusions:

  • Artemisinin resistance is a complex phenomenon driven by diverse molecular and cellular adaptations.
  • Understanding the interplay of cellular heterogeneity, environmental stress, and metabolic/transcriptional changes is vital for combating ART resistance.
Keywords:
PfKelch13Plasmodium falciparumartemisinin resistancemalariastress response

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