RIBOFLAVIN TRANSPORT IN TRIPANOSOMATIDS

BALCAZAR DE; BONOMI HR; VANRELL MC; ROMANO PS; CARRILLO C

Chascomus

Jornada; XVI Jornadas Anuales SAB; 2014

Sociedad Argentina de Biologìa

Trypanosoma cruzi, Trypanosoma brucei and Leishmania mexicana cause several diseases in humans. The current therapies are toxic and limited in efficacy, thus there is a need to identify targets to develop new treatments. Riboflavin (Rf) is an essential vitamin for all living cells. Metazoans obtain it from their diet through specific transporters. In this work we study Rf metabolism in the trypanosomatids T. brucei, L. Mexicana and, particularly, in T. cruzi and its life´s cycle. In silico analysis suggest that the three trypanosomatids are unable to synthesize Rf de novo, conversely their genomes encode for a putative permease which belongs to a novel family of Rf transporters. Proliferation is improved with increasing concentration of flavins and decreases in presence of Rf analogues. In T. cruzi, flavins also play an important role in metacyclogenesis, raising the number of trypomastigote per ml and Rf analogues impairing it. Moreover, Rf analogues have not affected infectivity but reduced the intracellular replication of amastigotes. In conclusion, flavins are essential for trypanosomatids, especially in T. cruzi, that incorporate it by specific transporter. This novel transporter family presents differences respect to the human, so it could be a potential target for development of new trypanocidal molecules.