Research projects

Parasite protozoa from the Leishmania genus are responsible of leishmaniasis. A set of diseases that causes from cutaneous alterations to visceral infection and death. The main responsible species in Southern Europe is L .infantum as well than in South America that induces a zoonotic visceral disease.  

Exosomes, extracelular vesicles produced bu cells as intercelular communication mechanism, have properties related with molecules contained in its cargo. Mainly lipids, proteins, mARN, and micro ARN. Leishmania spp. is able to produce exosomes probably related to the infection mechanism, that have been studied in the present project. We have studied the distinct components present into the exosomes cargo secreted by L. infantum along the different phases of the parasite infection. We have obtained vesicles from procyclic and metacyclic promastigotes as well as in amastigotes obtained from U937 cells infected in vitro.  We have found between other proteins, chaperones (hsp 70, hsp 83, hsp110) usually used as exosome biomarkers. Additionally, we detected the presence Ubiquitin proteasome components, as well as the methaloproteinase related to Leishmania infection gp63. In the case of intracellular infection, we have also found the presence of the enzyme malate dehydrogenase (LiMALDC). That enzyme interacts with tyrosine aminetranpherase of L.infantum (LiTAT) that has been putatively assigned a role as drug target. LiMALDC is able to oxidize the transamination product of LiTAT.  This methabolic route is essential for survival of the parasite. The presence of the enzyme into the exosomes cargo raises the possible role of this exovesicles in the maintenance of metabolic routes essential for the parasite survival along the infection process.

Infection by L. infantum specifically induces the expression into the exosomes of proteins related to apoptosis processes (anexin 5 and capases), cell adhesion, cytosqueleton or intercellular connections (integrins, desmoplaquin, etc,..). Stress related proteins such as hps70 or to the immune response like HLA-I related proteins, lectins, etc…are also present into the exosomes cargo.

We have also determined the RNA contain, both messenger and micro RNA, into the cargo of vesicles obtained from culture of both promastigote and amastigote forms from L. infantum. We have also obtained exosomes from the sera of hamsters infected with the parasite and from non-infected animals providing specific data on molecules present into infected animals.