Distinct physiological states of Plasmodium falciparum in malaria-infected patients

Abstract

Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment.

Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole

“…This phenomenon is in line with studies in the field where P. falciparum has been seen to exist in distinct physiological states, presumably changing its metabolic potential in response to environmental conditions. Although not fully understood, this could be a switch in emphasis from glycolysis to TCA metabolism for energy requirements when nutrients are scarce, for example in the hypoglycemic conditions that are common in malaria patients [95,96].…”

Identification of Novel Phenyl Butenonyl C-Glycosides with Ureidyl and Sulfonamidyl Moieties as Antimalarial Agents

“…Indeed, glucose is an essential energy substrate in many parasites, and they can undergo a metabolic shift in vivo, switching from predominately glycolytic metabolism to metabolism of alternative carbon sources through induction of gene sets combined with function of mitochondria and apicoplast. 12 Glucose delivery, however, is crucial for parasite survival and may also be critical for metabolic diversion of this key substrate from host tissues and thereby aggravating the disease processes. 13 Diphenyl propenones (chalcones), however, also exhibit antimalrial activity, 7,14−22 and malaria trophozoite cysteine protease has been proposed as possible target for this class of compound.…”

k-Means Walk: Unveiling Operational Mechanism of a Popular Clustering Approach for Microarray Data

“…An infectious disease with particular reference to malaria is caused by a lethal pathogenic protozoan, Plasmodium falciparum, responsible for major losses and death in Sub-Saharan Africa [4,5]. This disease has attracted intense microarray patronage with large data generation efforts [5][6][7][8][9][10][11][12][13]. In addition, from the effort of Kissinger et al [14] and Bahl et al [15], Plasmodium spp data are now accumulated and integrated into a database called PlasmoDB.…”