There is an urgent need to develop new treatments for Chagas' disease. To identify drug targets, it is important to understand the basic biology of Trypanosoma cruzi, in particular with respect to the biological pathways or proteins that are essential for its survival within the host. This review provides a streamlined approach for identifying drug targets using freely available chemogenetic databases and outlines the relevant characteristics of an ideal chemotherapeutic target. Among those are their essentiality, druggability, availability of structural information, and selectivity. At the moment only 16 genes have been found as essential by gene disruption in T. cruzi. At the TDR Targets database, a chemogenomics resource for neglected diseases, information about published structures for these genes was only found for three of these genes, and annotation of validated inhibitors was found in two. These inhibitors have activity against the parasitic stages present in the host. We then analyzed three of the pathways that are considered promising in the search for new targets: (1) Ergosterol biosynthesis, (2) Resistance to oxidative stress, (3) Synthesis of surface glycoconjugates. We have annotated all the genes that participate in them, identified those that are considered as druggable, and incorporated evidence from either Trypanosoma brucei, and Leishmania spp. that supports the hypothesis that these pathways are essential for T. cruzi survival.

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Apicomplexa are an extremely diverse group of unicellular organisms that infect humans and other animals. Despite the great advances in combating infectious diseases over the past century, these parasites still have a tremendous social and economic burden on human societies, particularly in tropical and subtropical regions of the world. Proteases from apicomplexa have been characterized at the molecular and cellular levels, and central roles have been proposed for proteases in diverse processes. In this work, 16 new genes encoding for trypsin proteases are identified in 8 apicomplexan genomes by a genome-wide survey. Phylogenetic analysis suggests that these genes were gained through both intracellular gene transfer and vertical gene transfer. Identification, characterization and understanding of the evolutionary origin of protease-mediated processes are crucial to increase the knowledge and improve the strategies for the development of novel chemotherapeutic agents and vaccines.

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The role and regulation of actin in Trypanosoma cruzi and other related parasites is largely unknown. Based on early genome analysis, it was proposed that there was a reduced dependency on the acto-myosin system in the trypanosomatid parasites. However, more recent studies have extended the set of potential actin regulatory proteins, particularly for T. cruzi. One of the identified actin-binding proteins in trypanosomatids is profilin. In other systems, it is capable of simultaneously binding both monomeric actin and several actin-regulatory factors. Hence, the study of profilin and its ligands may help to identify novel pathways in which actin is involved. In T. cruzi, profilin is encoded by a single copy gene. In this work, we demonstrated that this gene is constitutively expressed in both insect and mammalian stages of the parasite, and that the protein is diffusely distributed. Furthermore, we identified some of its potential ligands by LC-MS using GST-profilin pull-down assays of parasite's protein extracts. Many of them were trypanosomatid specific proteins with unknown functions, although proteins from the carbohydrate metabolism, and two metallopeptidases were also detected. As expected, known ligands of profilin in other organisms were identified, including actin, the microtubule components, and the elongation factor 1-alpha. Our work suggests that profilin and the actin system may be regulated by unknown factors and participate in novel biological processes.

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The Coleoptera Scarabaeidae family is one of the most diverse groups of insects on the planet, which live in complex microbiological environments. Their immune systems have evolved diverse families of Host Defense Peptides (HDP) with strong antimicrobial and immunomodulatory activities. However, there are several peptide sequences that await discovery in this group of organisms. This would pave the way to identify molecules with promising therapeutic potential. This work retrieved two sources of information: 1) De-novo transcriptomic data from two species of neotropical Scarabaeidae (Dichotomius satanas and Ontophagus curvicornis); 2) Sequence data deposited in available databases. A Blast-based search was conducted against the transcriptomes with a subset of sequences representative of the HDP. This work reports 155 novel HDP sequences identified in nine transcriptomes from seven species of Coleoptera: D. satanas (n = 76; 49.03%), O. curvicornis (n = 23; 14.83%), (Trypoxylus dichotomus) (n = 18; 11.61%), (Onthophagus nigriventris) (n = 10; 6.45%), (Heterochelus sp) (n = 6; 3.87%), (Oxysternon conspicillatum) (n = 18; 11.61%), and (Popillia japonica) (n = 4; 2.58%). These sequences were identified based on similarity to known HDP insect families. New members of defensins (n = 58; 37.42%), cecropins (n = 18; 11.61%), attancins (n = 41; 26.45%), and coleoptericins (n = 38; 24.52%) were described based on their physicochemical and structural characteristics, as well as their sequence relationship to other insect HDPs. Therefore, the Scarabaeidae family is a complex and rich group of insects with a great diversity of antimicrobial peptides with potential antimicrobial activity.

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