Comparison of the abilities of proteins from Bartonella bacilliformis and Bartonella henselae to deform red cell membranes and to bind to red cell ghost proteins

Abstract

Infections in humans by Bartonella bacilliformis, but not Bartonella henselae, are characterized by invasion of red cells. Supernatants of culture medium from B. bacilliformis and B. henselae each contain a protein which causes invagination of membranes of human red cells and formation of intracellular vacuoles. These two proteins are very similar in molecular mass, heat stability and mechanism of action. B. henselae does not bind to human red cells, but human red cell ghost membrane proteins were recognized by both bacteria, five by B. bacilliformis and the same five, and one additional protein by B. henselae. Two of these proteins had molecular masses consistent with actin and spectrin. Actin binds to five electroblotted outer membrane proteins from B. henselae and four of these proteins are retained on an actin-Sepharose column.

Intruders below the Radar: Molecular Pathogenesis of Bartonella spp

“…Other studies focused on the interaction of B. bacilliformis with host proteins on erythrocyte membranes, although it is not clear which interaction partners might serve as receptors for adhesion and which ones might possibly be involved in the invasion process. A first report showed that the sets of erythrocyte proteins bound by B. bacilliformis and B. henselae are remarkably similar and clearly include actin and spectrin (201), while a second study provided solid evidence that B. bacilliformis interacts with the ␣ and ␤ subunits of spectrin, band 3 protein, glycophorin A, and monomeric as well as dimeric glycophorin B (63), thereby specifying the previous results. Binding of B. bacilliformis to glycophorin B from solubilized erythrocytes was considerably enhanced if these had been treated with trypsin or neuraminidase before, but chemical removal of the carbohydrate moieties from erythrocytes abolished binding to all proteins (63).…”

“…It has been suggested that a secreted bacterial factor, deformin, would cause the membrane invaginations (440), but its molecular identity, mode of action, and secretion mechanism have remained elusive so far, although a well-documented phenomenology allows us to assemble a basic picture of its functionality. Importantly, deformation could also be demonstrated for B. henselae, making it likely to be a common feature of Bartonella erythrocyte infection (201).…”

“…Adhesion to erythrocytes as a first step of colonization was found to be a critical determinant of host specificity for the modern species (427) but apparently not for B. bacilliformis, since this species is known to adhere to cat erythrocytes (201), although it is restricted to infecting humans and closely related primates. Walker and Winkler reported that B. bacilliformis poorly adhered to human erythrocytes that had been treated with glucosidases, while the application of unspecific proteases (subtilisin or pronase) strongly favored adhesion (434).…”

“…Benson et al showed that erythrocytes developed progressing indentations and invaginations at the sites where B. bacilliformis attached (31), a process that is known as deformation and was also confirmed for B. henselae (201). The molecular mechanism underlying deformation and the contribution of a dedicated, small molecule from Bartonella (see "Deformin" below) have not been resolved so far, but it seems as if the pits on the erythrocyte surface would provide entry sites for Bartonella (31).…”

Infection of human CD34+ progenitor cells with Bartonella henselae results in intraerythrocytic presence of B henselae

“…11,12 Although it is known that Bartonella species invade erythrocytes in their animal reservoir hosts, 13 there is no evidence for a direct interaction of B henselae with human erythrocytes. 14 An in vivo model with similarities to human trench fever has been described, in which rats were infected intravenously with B tribocorum leading to intraerythrocytic presence of bacteria during the course of infection. 4 Bacteria were first detectable in erythrocytes 5 days after challenge with a peak between 10 and 14 days after infection.…”