Heavy metals are required by all organisms for normal function, but high levels of heavy metals are toxic. Therefore, homeostasis of these metals is crucial. In the human malaria-causing agent Plasmodium falciparum, the mechanisms of heavy metal transport have yet to be characterized. We have developed a P. falciparum line resistant to heavy metals from a wild-type line sensitive to heavy metals. A molecular and biochemical analysis of the involvement of the P. falciparum multidrug resistance 2 ( pfmdr2) gene, an ABC-type transporter, in heavy metal homeostasis was studied. Using a novel uptake assay applied on these two strains, it was demonstrated that, when exposed to heavy metals, the sensitive line accumulates metal, whereas no accumulation was observed in the resistant line. The accumulation occurs within the parasite itself and not in the cytoplasm of the red blood cell. This difference in the accumulation pattern is not a result of amplification of the pfmdr2 gene or of a change in the expression pattern of the gene in the two lines. Sequencing of the gene from both lines revealed a major difference; a stop codon is found in the sensitive line upstream of the normal termination, resulting in a truncated protein that lacks 188 amino acids that contain a portion of the essential cytoplasmatic transporter domain, thereby rendering it inactive. In contrast, the resistant line harbors a full-length, active protein. These findings strongly suggest that the PFMDR2 protein acts as an efflux pump of heavy metals.Malaria, caused in the majority of cases by the protozoan parasite Plasmodium falciparum, is a major global disease (1). Annual morbidity and mortality are estimated to reach overwhelming numbers of 300 -500 million and 1-3 million, respectively. In addition, malaria tolls a severe economic and social price, adding more afflictions to many third world countries already stricken by poverty and social unrest (2). Some of the reasons for this situation are the lack of an adequate vaccine and suitable antimalarial drugs, the latter due to the appearance of drug-resistant parasites. Our insufficient understanding of the biology of the malaria-causing agents limits our ability to vigorously combat this disease (1-3).A clear example of a poorly defined metabolic pathway of P. falciparum is its mechanism of heavy metal homeostasis. Heavy metals are defined as metals with a density higher than 5 g/cm 3 . Of 90 naturally occurring elements, 53 are heavy metals. Based on their solubility under physiological conditions, some 20 of them are available to living cells. Of these, only some are essential (iron, molybdenum, manganese, zinc, nickel, copper, vanadium, cobalt, and selenium), whereas the remaining ones appear in cells as a result of their wide distribution in various ecosystems. Regardless of their essentiality to life, most heavy metals are toxic to cells when their concentrations increase above a certain level. As such, mechanisms have evolved in different organisms to allow homeostasis of heavy metals. To d...

We present here the structure of a minicircle population based on transcriptome sequencing of Leptomonas pyrrhocoris. We show that minicircle DNA molecules are dimeric. As in dixenous species, the entire molecule of minicircle DNA is transcribed. This is the first minicircle transcriptome of monoxenous trypanosomatid species determined using NGS technology.