A yeast-based high-throughput screen identifies inhibitors of trypanosomatid HRG heme transporters with potent leishmanicidal and trypanocidal activity.

Objectives: New drugs are required to treat neglected diseases caused by trypanosomatid parasites such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi. An Achilles' heel of these parasites is their heme auxotrophy; they have an absolute dependence on scavenging this molecule from the host, and trypanosomatid HRG heme transporters (TrypHRG) play an important role in this process. As these proteins are essential for the parasites and have low similarity with their human orthologue, they have been proposed as attractive therapeutic targets.

FiCRoN, a deep learning-based algorithm for the automatic determination of intracellular parasite burden from fluorescence microscopy images.

Protozoan parasites are responsible for dramatic, neglected diseases. The automatic determination of intracellular parasite burden from fluorescence microscopy images is a challenging problem. Recent advances in deep learning are transforming this process, however, high-performance algorithms have not been developed.

New Insights on Heme Uptake in spp.

The protozoan parasite , responsible for leishmaniasis, is one of the few aerobic organisms that cannot synthesize the essential molecule heme. Therefore, it has developed specialized pathways to scavenge it from its host. In recent years, some proteins involved in the import of heme, such as HR1 and FLVCRB, have been identified, but relevant aspects regarding the process remain unknown.

Haem-responsive gene transporter enables mobilization of host haem in ticks.

Ticks, notorious blood-feeders and disease-vectors, have lost a part of their genetic complement encoding haem biosynthetic enzymes and are, therefore, dependent on the acquisition and distribution of host haem. Solute carrier protein SLC48A1, aka haem-responsive gene 1 protein (HRG1), has been implicated in haem transport, regulating the availability of intracellular haem. HRG1 transporter has been identified in both free-living and parasitic organisms ranging from unicellular kinetoplastids, nematodes, up to vertebrates.

Iron and Heme Metabolism at the Leishmania-Host Interface.

Species of the protozoan Leishmania are causative agents of human leishmaniasis, a disease that results in significant death, disability, and disfigurement around the world. The parasite is transmitted to a mammalian host by a sand fly vector where it develops as an intracellular parasite within macrophages. This process requires the acquisition of nutritional iron and heme from the host as Leishmania lacks the capacity for de novo heme synthesis and does not contain cytosolic iron-storage proteins.