Babesia and Human Babesiosis.

Babesia is a genus of intraerythrocytic protozoan parasites belonging to the exclusively parasitic phylum Apicomplexa [...].

Sickle Cell Anemia and Babesia Infection.

Babesia is an intraerythrocytic, obligate Apicomplexan parasite that has, in the last century, been implicated in human infections via zoonosis and is now widespread, especially in parts of the USA and Europe. It is naturally transmitted by the bite of a tick, but transfused blood from infected donors has also proven to be a major source of transmission. When infected, most humans are clinically asymptomatic, but the parasite can prove to be lethal when it infects immunocompromised individuals. Hemolysis and anemia are two common symptoms that accompany many infectious diseases, and this is particularly true of parasitic diseases that target red cells. Clinically, this becomes an acute problem for subjects who are prone to hemolysis and depend on frequent transfusions, like patients with sickle cell anemia or thalassemia. Little is known about Babesia's pathogenesis in these hemoglobinopathies, and most parallels are drawn from its evolutionarily related Plasmodium parasite which shares the same environmental niche, the RBCs, in the human host. In vitro as well as in vivo Babesia-infected mouse sickle cell disease (SCD) models support the inhibition of intra-erythrocytic parasite proliferation, but mechanisms driving the protection of such hemoglobinopathies against infection are not fully studied. This review provides an overview of our current knowledge of Babesia infection and hemoglobinopathies, focusing on possible mechanisms behind this parasite resistance and the clinical repercussions faced by Babesia-infected human hosts harboring mutations in their globin gene.

Babesia divergens and Plasmodium falciparum use common receptors, glycophorins A and B, to invade the human red blood cell.

Babesiosis has long been recognized as an economically important disease of cattle, but only in the last 30 years has Babesia been recognized as an important pathogen in humans. Invasion of erythrocytes is an integral part of the Babesia life cycle. However, very little information is available on the molecules involved in this process, in contrast to another hemoparasite, Plasmodium falciparum. Using invasion assays into normal red blood cells (RBCs), enzyme-treated cells, and clinically mutant cells, we showed that Babesia divergens uses neuraminidase- and trypsin-sensitive receptors to enter the RBCs, of which glycophorins A and B are the prominent ones. These results could have broad implications relating to evolutionarily conserved mechanisms of host cell entry in these related Apicomplexan parasites and pave the way toward a detailed molecular analysis of erythrocyte invasion in B. divergens.

Invasion profiles of Brazilian field isolates of Plasmodium falciparum: phenotypic and genotypic analyses.

The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a-) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.

Characterization of PfRhop148, a novel rhoptry protein of Plasmodium falciparum.

Rhoptries are apical organelles which play an important role in erythrocytic invasion. A Plasmodium falciparum cDNA clone, coding for a novel rhoptry protein PfRhop148, was obtained by antibody screening of a library. The deduced amino acid sequence consists of 1262 amino acids and is highly rich in Asn (22%). The Asn residues are distributed in clusters and in multiple units of repeats. Analysis of specific RNA transcript and protein showed that PfRhop148 was synthesized at around 21 h post-invasion. IFA and immunoelectron microscopic analyses revealed a rhoptry localization for the protein. The role of this protein in invasion and its relationship to the RhopH complex is now under further investigation.

Glycophorin C is the receptor for the Plasmodium falciparum erythrocyte binding ligand PfEBP-2 (baebl).

We report in this paper that glycophorin C (GPC) is the receptor for PfEBP-2 (baebl, EBA-140), the newly identified erythrocyte binding ligand of Plasmodium falciparum. PfEBP-2 is a member of the Duffy binding-like erythrocyte binding protein (DBL-EBP) family. Although several reports have been published characterizing PfEBP-2, the identity of its erythrocytic receptor was still unknown. Using a combination of enzymatically treated red blood cells (RBCs) and rare, variant RBCs lacking different surface proteins, we have shown that PfEBP-2 does not bind to cells lacking GPC. Additionally, we found that PfEBP-2 binds differentially to variants of GPC lacking exon 2 or exon 3, and determined that the binding domain on GPC is potentially restricted to amino acid residues 14 through 22 within exon 2. Thus PfEBP-2 is involved in a sialic acid-dependent pathway of invasion, which does not involve glycophorin A or glycophorin B and represents a novel route of entry into the RBCs.