Trypanosoma cruzi RNA-binding protein DRBD3: perinuclear foci formation during benznidazole exposure.

Benznidazole (BZ) is the trypanocidal compound of choice for Chagas disease, a neglected tropical disease in the Americas. However, this drug often fails to cure the infection. The regulation of gene expression in Trypanosoma cruzi, the causative agent of Chagas disease, is based on post-transcriptional mechanisms.

Metformin Treatment Modulates Long Non-Coding RNA Isoforms Expression in Human Cells.

Long noncoding RNAs (lncRNAs) undergo splicing and have multiple transcribed isoforms. Nevertheless, for lncRNAs, as well as for mRNA, measurements of expression are routinely performed only at the gene level. Metformin is the first-line oral therapy for type 2 diabetes mellitus and other metabolic diseases.

Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.

The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group.

Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation in Exposed to Oxidative Agent.

parasites are the causative agents of a group of neglected tropical diseases known as leishmaniasis. The molecular mechanisms employed by these parasites to adapt to the adverse conditions found in their hosts are not yet completely understood. DNA repair pathways can be used by to enable survival in the interior of macrophages, where the parasite is constantly exposed to oxygen reactive species.

DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in .

DNA topoisomerases are enzymes that modulate DNA topology. Among them, topoisomerase 3α is engaged in genomic maintenance acting in DNA replication termination, sister chromatid separation, and dissolution of recombination intermediates. To evaluate the role of this enzyme in , the etiologic agent of Chagas disease, a topoisomerase 3α knockout parasite (TcTopo3α KO) was generated, and the parasite growth, as well as its response to several DNA damage agents, were evaluated.

Importance of Angomonas deanei KAP4 for kDNA arrangement, cell division and maintenance of the host-bacterium relationship.

Angomonas deanei coevolves in a mutualistic relationship with a symbiotic bacterium that divides in synchronicity with other host cell structures. Trypanosomatid mitochondrial DNA is contained in the kinetoplast and is composed of thousands of interlocked DNA circles (kDNA). The arrangement of kDNA is related to the presence of histone-like proteins, known as KAPs (kinetoplast-associated proteins), that neutralize the negatively charged kDNA, thereby affecting the activity of mitochondrial enzymes involved in replication, transcription and repair.

Differential Modulation of Mouse Heart Gene Expression by Infection With Two Strains: A Transcriptome Analysis.

The protozoan () is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system.

Mitochondrial behavior during nuclear and mitochondrial DNA repair in Trypanosoma cruzi epimastigotes.

Different genotoxic agents can lead to DNA single- and double-strand breaks, base modification and oxidation. As most living organisms, Trypanosoma cruzi is subjected to oxidative stress during its life cycle; thus, DNA repair is essential for parasite survival and establishment of infection. The mitochondrion plays important roles beyond the production of ATP.

The heterologous expression of Escherichia coli MutT enzyme is involved in the protection against oxidative stress in Leishmania braziliensis.

BACKGROUND Oxidative stress is responsible for generating DNA lesions and the 8-oxoguanine (8-oxoG) is the most commonly lesion found in DNA damage. When this base is incorporated during DNA replication, it could generate double-strand DNA breaks and cellular death. MutT enzyme hydrolyzes the 8-oxoG from the nucleotide pool, preventing its incorporation during DNA replication.

DNA lesions and repair in trypanosomatids infection.

Pathological processes such as bacterial, viral and parasitic infections can generate a plethora of responses such as, but not restricted to, oxidative stress that can be harmful to the host and the pathogen. This stress occurs when there is an imbalance between reactive oxygen species produced and antioxidant factors produced in response to the infection. This imbalance can lead to DNA lesions in both infected cells as well as in the pathogen.

The Influence of Recombinational Processes to Induce Dormancy in .

The protozoan is the causative agent of Chagas disease, a neglected tropical disease that affects around 8 million people worldwide. Chagas disease can be divided into two stages: an acute stage with high parasitemia followed by a low parasitemia chronic stage. Recently, the importance of dormancy concerning drug resistance in amastigotes has been shown.

Trypanosoma cruzi RNA-binding protein ALBA30 aggregates into cytoplasmic foci under nutritional stress.

Trypanosoma cruzi, the causative agent of Chagas disease, has a complex life cycle that requires the adaptation to different environments. In the absence of traditional mechanisms for regulation of gene expression, this parasite relies on posttranscriptional control events, which allow the progression of its life cycle in different hosts and stress conditions. In this context, different stress conditions trigger the aggregation of RNA-binding proteins and their target mRNAs into cytoplasmic foci known as RNA granules, which act as RNA-sorting centers.

Analysis of DNA Exchange Using Thymidine Analogs (ADExTA) in .

is a protozoan parasite belonging to the Trypanosomatidae family. Although the trypanosomatids multiply predominantly by clonal generation, the presence of DNA exchange in some of them has been puzzling researchers over the years, mainly because it may represent a novel form that these organisms use to gain variability. Analysis of DNA Exchange using Thymidine Analogs (ADExTA) is a method that allows the detection and measurement of rates of DNA exchange, particularly in trypanosomatid cells, in a rapid and simple manner by indirect immunofluorescence assay (IFA).

The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.

In Trypanosoma cruzi, the etiologic agent of Chagas disease, Rad51 (TcRad51) is a central enzyme for homologous recombination. Here we describe the different roles of TcRad51 in DNA repair. Epimastigotes of T.

Selective human inhibitors of ATR and ATM render Leishmania major promastigotes sensitive to oxidative damage.

All cellular processes, including those involved in normal cell metabolism to those responsible for cell proliferation or death, are finely controlled by cell signaling pathways, whose core proteins constitute the family of phosphatidylinositol 3-kinase-related kinases (PIKKs). Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3 related (ATR) are two important PIKK proteins that act in response to DNA damage, phosphorylating a large number of proteins to exert control over genomic integrity. The genus Leishmania belongs to a group of early divergent eukaryotes in evolution and has a highly plastic genome, probably owing to the existence of signaling pathways designed to maintain genomic integrity.

Assessment of genetic mutation frequency induced by oxidative stress in Trypanosoma cruzi.

Trypanosoma cruzi is the etiological agent of Chagas disease, a public health challenge due to its morbidity and mortality rates, which affects around 6-7 million people worldwide. Symptoms, response to chemotherapy, and the course of Chagas disease are greatly influenced by T. cruzi's intra-specific variability.

Vaccination With Recombinant Filamentous Phages Against Parasite Infection Requires TLR9 Expression.

Recombinant filamentous bacteriophages (r) expressing antigenic peptides were shown to induce cell-mediated immune responses in the absence of added adjuvant, being a promising delivery system for vaccination. Here, we tested the capacity of r phages to protect against infection with the human protozoan , the etiologic agent of Chagas Disease. For this, C57BL/6 (B6) and mice were vaccinated with r phages expressing the OVA peptide or the -immunodominant peptides PA8 and TSKB20 and challenged with either the Y-OVA or Y-strain, respectively.

Landscape of the spliced leader trans-splicing mechanism in Schistosoma mansoni.

Spliced leader dependent trans-splicing (SLTS) has been described as an important RNA regulatory process that occurs in different organisms, including the trematode Schistosoma mansoni. We identified more than seven thousand putative SLTS sites in the parasite, comprising genes with a wide spectrum of functional classes, which underlines the SLTS as a ubiquitous mechanism in the parasite. Also, SLTS gene expression levels span several orders of magnitude, showing that SLTS frequency is not determined by the expression level of the target gene, but by the presence of particular gene features facilitating or hindering the trans-splicing mechanism.

Prostaglandin F2α synthase in plays critical roles in oxidative stress and susceptibility to benznidazole.

Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2α synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mechanism of action of Bz is uncertain.

UvrB protein of Corynebacterium pseudotuberculosis complements the phenotype of knockout Escherichia coli and recognizes DNA damage caused by UV radiation but not 8-oxoguanine in vitro.

In prokaryotic cells, the UvrB protein plays a central role in nucleotide excision repair, which is involved in the recognition of bulky DNA lesions generated by chemical or physical agents. The present investigation aimed to characterize the uvrB gene of Corynebacterium pseudotuberculosis (CpuvrB) and evaluate its involvement in the DNA repair system of this pathogenic organism. In computational analysis, the alignment of the UvrB protein sequences of Escherichia coli, Mycobacterium tuberculosis, Bacillus caldotenax and Corynebacterium pseudotuberculosis showed high similarity and the catalytic amino acid residues and functional domains are preserved.