Caracterização morfológica e bioquímica de uma linhagem mutante de Leishmania braziliensis resistente à tunicamicina

Abstract

Leishmaniasis is a group of diseases caused by parasites of the Leishmania type and is of great importance in public health. Disease control is still a challenge due to its resistance to the drugs used in treatment. In this context, the study of potential resistance is essential for the exploration of the potential metabolism of parasitism and improve the structures of the drugs of the stress of drugs In this study, a mutant strain of Leishmania braziliensis resistant to the antibiotic tunicamycin, a drug that inhibits the glycosylation of protein, was generated by the gradual increase in drug concentration (stepwise). In order to evaluate the metabolic adaptations caused during the process of developing resistance to tunicamycin. In order to evaluate the metabolic changes during the acquisition of resistance to tunicamycin, genomic analyzes, microscopy, infectivity, cytometry and resistance metabolism analysis were performed. Promastigotes of Leishmania braziliensis resistant to tunicamycin (up to 80 times the value of LD50), gene amplification and a concomitant increase in virulence. Morphological changes were observed in the lineage such, disorganization of cisterns of the Golgi complex, changes in the process of protein glycosylation. Changes in the metabolism of various carbon sources, related to the production of substrate for a synthesis of fatty acid, molecules that play an important role in the glycosylation of proteins, were detected as responses to the induction blocking process of tunicamycin. The results suggests that main mechanisms of drug resistance, as well as the influence of protein glycosylation on host parasitic infections in Leishmania.