Nilmar Moretti

Nilmar Moretti
Universidade Federal de São Paulo | UNIFESP · Departamento de Microbiologia, Imunologia e Parasitologia

PhD
Professor at Federal University of Sao Paulo - Brazil, working with protein posttranslational modifications in parasites

About

44
Publications
7,105
Reads
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434
Citations
Education
March 2007 - March 2012
Faculdade de Medicina de Ribeirao Preto - USP
Field of study
  • Molecular and Cellular Biology
March 2003 - December 2007

Publications

Publications (44)
Article
The selection of Leishmania hybrids in axenic culture was considered rare until recently, when Louradour and Ferreira et al., demonstrated that induced DNA damage facilitates genetic exchange, resulting in full genome tetraploid progenies in vitro. Meiosis-related gene homologues HAP2, GEX1, and RAD51 were found to be involved, opening new avenues...
Article
Full-text available
Despite the increasing number of manuscripts describing potential alternative antileishmanial compounds, little is advancing on translating these knowledges to new products to treat leishmaniasis. This is in part due to the lack of standardisations during pre-clinical drug discovery stage and also depends on the alignment of goals among universitie...
Article
Full-text available
Trans-sialidases (TS) are unusual enzymes present on the surface of Trypanosoma cruzi, the causative agent of Chagas disease. Encoded by the largest gene family in the T. cruzi genome, only few members of the TS family have catalytic activity. Active trans-sialidases (aTS) are responsible for transferring sialic acid from host glycoconjugates to mu...
Article
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The flagellum of Trypanosomatids is an organelle that contributes to multiple functions, including motility, cell division, and host-pathogen interaction. Trypanin was first described in Trypanosoma brucei and is part of the dynein regulatory complex. TbTrypanin knockdown parasites showed motility defects in procyclic forms; however, silencing in b...
Article
Full-text available
Despite the increasing number of manuscripts describing potential alternative antileishmanial compounds, little is advancing on translating these knowledges to new products to treat leishmaniasis. This is in part due to the lack of standardisations during pre-clinical drug discovery stage and also depends on the alignment of goals among universitie...
Article
Full-text available
Trypanosoma cruzi faces a variety of environmental scenarios during its life cycle, which include changes in the redox environment that requires a fine regulation of a complex antioxidant arsenal of enzymes. Reversible posttranslational modifications, as lysine acetylation, are a fast and economical way for cells to react to environmental condition...
Preprint
Full-text available
Trypanosoma cruzi, the etiological agent of Chagas disease, faces a variety of environmental scenarios during its life cycle in both invertebrate and vertebrate hosts, which include changes in the redox environment that requires a fine regulation of a complex antioxidant arsenal of enzymes. Reversible post-translational modifications, as lysine ace...
Article
Parasitic diseases affect millions of individuals worldwide, mainly in low-income regions. There is no cure for most of these diseases, and the treatment relies on drugs that have side effects and lead to drug resistance, emphasizing the urgency to find new treatments. Snake venom has been gaining prominence as a rich source of molecules with antip...
Article
The cell biology of a parasitic protozoan as well as the impact of the infection in host cells can be addressed using genome modification techniques. The development of robust methods eases the burden to obtain gene mutants and contributes to answer specific biological questions. Here we describe the LeishGEdit CRISPR-Cas9 high- throughput method t...
Article
Full-text available
Trypanosoma and Leishmania parasites cause devastating tropical diseases resulting in serious global health consequences. These organisms have complex life cycles with mammalian hosts and insect vectors. The parasites must therefore survive in different environments, demanding rapid physiological and metabolic changes. These responses depend upon r...
Article
Protein lysine acetylation has emerged as a major regulatory post-translational modification in different organisms, present not only on histone proteins affecting chromatin structure and gene expression but also on nonhistone proteins involved in several cellular processes. The same scenario was observed in protozoan parasites after the descriptio...
Article
Our understanding of regulatory factors in Leishmania differentiation has long been restricted by the available genetic tools, but the availability of CRISPR/Cas9 has changed the landscape forever. Recently, Baker and Catta-Preta et al. applied Cas9 editing and kinome-wide bar-seq to dissect the function of 204 kinases in the Leishmania mexicana li...
Article
Infection by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, depends on reactive oxygen species (ROS), which has been described to induce parasite proliferation in mammalian host cells. It is unknown how the parasite manages to increase host ROS levels. Here, we found that intracellular T. cruzi forms release in the host cytos...
Article
Full-text available
Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, a↵ecting more than 7 million people in the world. Benznidazole and nifurtimox are the only drugs available for treatment and in addition to causing several side e↵ects, are only satisfactory in the acute phase of the disease. Sirtuins are NAD +-dependent deacetylases i...
Article
Full-text available
Post-translational modifications provide suitable mechanisms for cellular adaptation to environmental changes. Lysine acetylation is one of these modifications and occurs with the addition of an acetyl group to Nε-amino chain of this residue, eliminating its positive charge. Recently, we found distinct acetylation profiles of procyclic and bloodstr...
Article
Full-text available
The drugs currently used to treat leishmaniases have limitations concerning cost, efficacy and safety, making urgent the search for new therapeutic approaches. We found that the complexes were active against L. infantum and L. braziliensis intracellular amastigotes with IC50 values ranging from 0.5 to 5.5 μM. All complexes were potent inhibitors of...
Article
Human trypanosomiasis and leishmaniasis are vector‐borne neglected tropical diseases caused by infection with the protozoan parasites Trypanosoma spp. and Leishmania spp., respectively. Once restricted to endemic areas, these diseases are now distributed worldwide due to human migration, climate change, and anthropogenic disturbance, causing signif...
Article
In recent years, the intensification of the use of immunosuppressive therapies has increased the incidence of invasive infections caused by opportunistic fungi. Considering that, the spread of azole resistance and amphotericin B (AmB) inefficiency against some clinical and environmental isolates has been described. Thus, to avoid a global problem w...
Article
Dot1 enzymes are histone methyltransferases that mono-, di- and trimethylate lysine 79 of histone H3 to affect several nuclear processes. The functions of these different methylation states are still largely unknown. Trypanosomes, which are flagellated protozoa that cause several parasitic diseases, have two Dot1 homologues. Dot1A catalyzes the mon...
Article
Chronic lymphocytic leukemia (CLL) is a chronic form of leukemia that originates from an abnormal expansion of CD5+B‐1 cells. Deregulation in the BCR signaling is associated with B‐cell transformation. Contrariwise to B‐2 cells, BCR engagement in B‐1 cells results in low proliferation rate and increased apoptosis population, whereas overactivation...
Article
Full-text available
Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator...
Preprint
Full-text available
The drugs currently used to treat leishmaniasis have limitations concerning cost, efficacy and safety, making urgent the search for new therapeutic approaches. Here we report the antileishmanial activity of 14 gold(I) complexes. We found that the complexes were active against L. infantum and L. braziliensis intracellular amastigotes with IC50 value...
Article
Full-text available
Sporotrichosis is a mycosis that affects the skin, lymphatic system and other organs in humans and animals. The disease has a worldwide distribution, with endemic areas in Brazil, and is caused by a complex of species, including Sporothrix brasiliensis. Some fungi release extracellular vesicles (EVs) that can interact with the host cell and modulat...
Article
Full-text available
Protein acetylation is a post-translational modification regulating diverse cellular processes. By using proteomic approaches we identified N-terminal and ε-lysine acetylated proteins in Trypanosoma cruzi and Trypanosoma brucei, which are protozoan parasites that cause significant human and animal diseases. We detected 288 lysine acetylation sites...
Article
Ikaros is a broad transcription factor pointed as a critical regulator of lymphocyte development. Recent reports have emphasized that distinct isoforms of Ikaros control the dichotomy of the hematopoietic system into lymphoid and myeloid lineages. In addition, expression of dominant-negative isoforms of Ikaros is linked to abnormal hematopoiesis, w...
Article
Full-text available
Trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi's antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which...
Chapter
Full-text available
Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp. are etiological agents of the following neglected diseases: African sleeping sickness (T. brucei), Chagas’ disease (T. cruzi) and leishmaniasis (Leishmania spp.). These parasites are eukaryotic cells that diverged early in evolution and therefore harbor modified organelles, such as glycosome...
Article
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The advance in biochemical and microscopy techniques has revealed the complexity and intricate nucleoplasm structure. Several subcompartments were identified in nucleus and the importance of these subcompartments in processes crucial for normal nuclear activity has been demonstrated. In this mini-review, we will give an overview about the compositi...
Article
Full-text available
Kinetoplastids cause Chagas disease, human African trypanosomiasis, and leishmaniases. Current treatments for these diseases are toxic and inefficient, and our limited knowledge of drug targets and inhibitors has dramatically hindered the development of new drugs. Here we used a chemogenetic approach to identify new kinetoplastid drug targets and i...
Article
Full-text available
Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathogens rely on chitinases for successful parasitization. Here, we purified and characterized a chit...
Article
Full-text available
The histone H4 from Trypanosomatids diverged from other eukaryotes in the N-terminus, a region that undergoes post-translation modifications involved in the control of gene expression, DNA replication, and chromatin assembly. Nonetheless, the N-terminus of Trypanosoma cruzi histone H4 is mainly acetylated at lysine 4. The lysines 10 and 14 are also...
Article
Full-text available
Acetylation of lysine is a major post-translational modification of proteins that is catalyzed by lysine acetyltransferases, while lysine deacetylases remove the acetyl groups. Amongst the deacetylases, the sirtuins are NAD(+)-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin specific i...
Article
Full-text available
Prior studies have highlighted the potential of superoxide dismutases as drug targets in eukaryotic pathogens. This report presents the structures of three iron-dependent superoxide dismutases (FeSODs) from Trypanosoma cruzi, Leishmania major and Babesia bovis. Comparison with existing structures from Plasmodium and other trypanosome isoforms shows...
Article
Full-text available
Translation initiation has been described as a key step for the control of growth and differentiation of several protozoan parasites in response to environmental changes. This occurs by the activation of protein kinases that phosphorylate the alpha subunit of the translation initiation factor 2 (eIF2α), which decreases translation, and in higher eu...
Article
Full-text available
The phosphorylation of the carboxy-terminal heptapeptide repeats of the largest subunit of RNA polymerase II (Pol II) controls several transcription-related events in eukaryotes. Trypanosomatids lack these typical repeats and display an unusual transcription control. RNA Pol II associates with the transcription site of the spliced leader (SL) RNA,...
Article
Full-text available
Trypanosomatids are parasites of worldwide distribution with relevant importance in human and veterinary health, which inhabit invertebrate and vertebrate hosts, such that they are exposed to large environmental variations during their life cycle. The signaling mechanisms and molecular basis that lead these parasites to adjust to such distinct cond...

Projects

Projects (2)
Project
The main goal of this project is to understand the function of protein acetylation in the regulation of key cellular processes of eukaryotic pathogens, specially protozoan parasites, such as Leishmania, Trypanosoma cruzi and Trypanosoma brucei. Also, to explore the enzymes that regulate this modification as drug targets for development of new treatments.