Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.

A significant percentage of exogenous cholesterol was found in promastigotes and amastigotes of all studied species of Leishmania, suggesting a biological role for this molecule. Previous studies have shown that promastigotes of Leishmania uptake more low-density lipoprotein (LDL) particles under pharmacological pressure and are more susceptible to ergosterol inhibition in the absence of exogenous sources of cholesterol. This work shows that the host's LDL is available to intracellular amastigotes and that the absence of exogenous cholesterol enhances the potency of sterol biosynthesis inhibitors in infected macrophages. A complete understanding of cholesterol transport to the parasitophorous vacuole can guide the development of a new drug class to be used in combination with sterol biosynthesis inhibitors for the treatment of leishmaniases.

Lipoproteins from vertebrate host blood plasma are involved in Trypanosoma cruzi epimastigote agglutination and participate in interaction with the vector insect, Rhodnius prolixus.

Chagas disease, infecting ca. 8 million people in Central and South America, is mediated by the protozoan parasite, Trypanosoma cruzi. The parasite is transmitted by the bite of blood sucking triatomine insects, such as Rhodnius prolixus, that had previously fed on parasite-infected vertebrate blood and voided their contaminated feces and urine into the wound. The stages of the parasite life cycle in both the insect vector and human host are well-known, but determinants of infection in the insect gut are complex and enigmatic. This paper examines the possible role of the R. prolixus gut agglutinins in the parasite life cycle. The results, derived from gut extracts made from R. prolixus fed on various diets with different vertebrate blood components, and cross adsorption experiments, showed for the first time that R. prolixus has two distinct gut agglutinins originating from their vertebrate blood meal, one for T. cruzi (the parasite agglutinin, PA) and the other for the erythrocytes (the hemagglutinin, HA). Again, uniquely, the results also demonstrate that these two agglutinins are derived, respectively, from the plasma and erythrocyte components of the vertebrate blood. Subsequent experiments, examining in more detail the nature of the plasma components forming the T. cruzi PA, used fractionated extracts of the vertebrate plasma (high density lipoprotein, HDL; low density lipoprotein, LDL, and delipidated plasma) in agglutination assays. The results confirmed the identity of the PA as a high density lipoprotein (HDL) in the plasma of the vertebrate blood meal which agglutinates parasites in the R. prolixus gut. In addition, the use of single or double labeled HDL in fluorescence and confocal microscopy showed the interaction of the labeled HDL with the parasite surface and its internalization at later times. Finally, results of T. cruzi parasitization of R. prolixus, incorporating various vertebrate blood components, resulted in highly significant increases in infectivity in the presence of HDL from the 2nd day of infection, thus confirming the important role of this molecule in T. cruzi infection of R. prolixus.