Search

Background: Strigomonas culicis is a monoxenic trypanosomatid parasite of insects that naturally contains an endosymbiotic bacterium. The aposymbiotic strain can be obtained, making this strain a model for evolutive research about organelle origins. In addition, S. culicis contains homologues of virulence factors of pathogenic trypanosomatids, which functions are waiting for further analysis. In this sense, the publication of S. culicis proteome makes feasible additional investigations regarding the differential expression of peptidases from the wild-type (WT) and the aposymbiotic (APO) strains., Objectives: Here, we analysed two proteomic data from S. culicis WT and APO strains screening for peptidases differentially expressed and assessed the differential expression of cysteine and metallopeptidases., Methods: A comparative proteomic screening between WT and APO identified 43 modulated peptidases., Findings: Cysteine and metallopeptidases, such as calpains and GP63, were the major classes, highlighting their significance. GP63 exhibited an increased proteolysis in a specific metallopeptidase substrate, an up-modulation gene expression in RT-PCR, and a higher protein identification by flow cytometry in the aposymbiotic strain. Notwithstanding, the wild-type strain showed enhanced cysteine peptidase activity., Main Conclusion: Our study highlighted the endosymbiont influence in S. culicis peptidase expression, with GP63 expression and activity raised in the aposymbiotic strain, whereas cysteine peptidase levels were reduced.

The trypanosomatids Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are etiological agents of important neglected tropical diseases, affecting millions of people worldwide, and the drugs available for these diseases present several limitations. Novel efficient and nontoxic drugs are necessary as an alternative to the current chemotherapy. The unique mitochondrion of trypanosomatids and its peculiar features turn this organelle a potential drug target. Several phenotypic studies describe the damage in the parasite mitochondrial ultrastructure, but the molecular target is unknown. Few reports demonstrated the electron transport system (ETS) as a target due to the high similarities to mammalian orthologues, hence ETS is not a good candidate for drug intervention. On the other hand, antioxidant enzymes, such as trypanothione reductase, and an alternative oxidase (AOX) seem to be interesting targets; however no high active inhibitors were developed up to now. Finally, due to the remarkable differences to mammalian machinery, together with the high biological importance for the parasite survival, the mitochondrial import system stands out as a very promising target in trypanosomatids. Archaic translocase of the outer membrane (ATOM) and translocase of the inner membrane (TIM) complexes, which mediate both protein and tRNA import, composed by specific subunits of these parasites, could be excellent candidates, deserving studies focused on the development of specific drugs.