Publications by authors named "Y Romina Nievas"

6 Publications

  • Page 1 of 1

Extracellular vesicles released by anaerobic protozoan parasites: Current situation.

Cell Microbiol 2020 11 10;22(11):e13257. Epub 2020 Sep 10.

Laboratorio de Parásitos Anaerobios, Instituto Tecnológico Chascomús (INTECH), CONICET-UNSAM, Chascomús, Argentina.

Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism for transferring information between cells and organisms across all three kingdoms of life. Parasitic unicellular eukaryotes use EVs as vehicles for intercellular communication and host manipulation. Pathogenic protozoans are able to modulate the immune system of the host and establish infection by transferring a wide range of molecules contained in different types of EVs. In addition to effects on the host, EVs are able to transfer virulence factors, drug-resistance genes and differentiation factors between parasites. In this review we cover the current knowledge on EVs from anaerobic or microaerophilic extracellular protozoan parasites, including Trichomonas vaginalis, Tritrichomonas foetus, Giardia intestinalis and Entamoeba histolytica, with a focus on their potential role in the process of infection. The role of EVs in host: parasite communication adds a new level of complexity to our understanding of parasite biology, and may be a key to understand the complexity behind their mechanism of pathogenesis.
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http://dx.doi.org/10.1111/cmi.13257DOI Listing
November 2020

Essential roles for deubiquitination in Leishmania life cycle progression.

PLoS Pathog 2020 06 16;16(6):e1008455. Epub 2020 Jun 16.

York Biomedical Research Institute and Department of Biology, University of York, United Kingdom.

The parasitic protozoan Leishmania requires proteasomal, autophagic and lysosomal proteolytic pathways to enact the extensive cellular remodelling that occurs during its life cycle. The proteasome is essential for parasite proliferation, yet little is known about the requirement for ubiquitination/deubiquitination processes in growth and differentiation. Activity-based protein profiling of L. mexicana C12, C19 and C65 deubiquitinating cysteine peptidases (DUBs) revealed DUB activity remains relatively constant during differentiation of procyclic promastigote to amastigote. However, when life cycle phenotyping (bar-seq) was performed on a pool including 15 barcoded DUB null mutants created in promastigotes using CRISPR-Cas9, significant loss of fitness was observed during differentiation and intracellular infection. DUBs 4, 7, and 13 are required for successful transformation from metacyclic promastigote to amastigote and DUBs 3, 5, 6, 8, 10, 11 and 14 are required for normal amastigote proliferation in mice. DUBs 1, 2, 12 and 16 are essential for promastigote viability and the essential role of DUB2 in establishing infection was demonstrated using DiCre inducible gene deletion in vitro and in vivo. DUB2 is found in the nucleus and interacts with nuclear proteins associated with transcription/chromatin dynamics, mRNA splicing and mRNA capping. DUB2 has broad linkage specificity, cleaving all the di-ubiquitin chains except for Lys27 and Met1. Our study demonstrates the crucial role that DUBs play in differentiation and intracellular survival of Leishmania and that amastigotes are exquisitely sensitive to disruption of ubiquitination homeostasis.
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http://dx.doi.org/10.1371/journal.ppat.1008455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319358PMC
June 2020

Protein Palmitoylation Plays an Important Role in Adherence.

Mol Cell Proteomics 2018 11 14;17(11):2229-2241. Epub 2018 Feb 14.

From the ‡Laboratorio de Parásitos Anaerobios, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús (IIB-INTECH), CONICET-UNSAM, Chascomús B7130IWA, Argentina;

The flagellated protozoan parasite is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in In order to study the extent and function of S-acylation in biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of pathogenesis.
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http://dx.doi.org/10.1074/mcp.RA117.000018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210223PMC
November 2018

Membrane-shed vesicles from the parasite Trichomonas vaginalis: characterization and their association with cell interaction.

Cell Mol Life Sci 2018 06 8;75(12):2211-2226. Epub 2017 Dec 8.

Laboratorio de Parásitos Anaerobios Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús (IIB-INTECH), CONICET-UNSAM, Intendente Marino KM 8.200 Chascomús, B7130IWA, Chascomús, Provincia de Buenos Aires, Argentina.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor-ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.
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http://dx.doi.org/10.1007/s00018-017-2726-3DOI Listing
June 2018

Epigenetics regulates transcription and pathogenesis in the parasite Trichomonas vaginalis.

Cell Microbiol 2017 06 22;19(6). Epub 2017 Jan 22.

Laboratorio de Parásitos Anaerobios, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús (IIB-INTECH), CONICET-UNSAM, Chascomús, Argentina.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Different T. vaginalis strains vary greatly in their adherence and cytolytic capacities. These phenotypic differences might be attributed to differentially expressed genes as a consequence of extra-genetic variation, such as epigenetic modifications. In this study, we explored the role of histone acetylation in regulating gene transcription and pathogenesis in T. vaginalis. Here, we show that histone 3 lysine acetylation (H3KAc) is enriched in nucleosomes positioned around the transcription start site of active genes (BAP1 and BAP2) in a highly adherent parasite strain; compared with the low acetylation abundance in contrast to that observed in a less-adherent strain that expresses these genes at low levels. Additionally, exposition of less-adherent strain with a specific histone deacetylases inhibitor, trichostatin A, upregulated the transcription of BAP1 and BAP2 genes in concomitance with an increase in H3KAc abundance and chromatin accessibility around their transcription start sites. Moreover, we demonstrated that the binding of initiator binding protein, the transcription factor responsible for the initiation of transcription of ~75% of known T. vaginalis genes, depends on the histone acetylation state around the metazoan-like initiator to which initiator binding protein binds. Finally, we found that trichostatin A treatment increased parasite aggregation and adherence to host cells. Our data demonstrated for the first time that H3KAc is a permissive histone modification that functions to mediate both transcription and pathogenesis of the parasite T. vaginalis.
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http://dx.doi.org/10.1111/cmi.12716DOI Listing
June 2017

The C-terminal tail of tetraspanin proteins regulates their intracellular distribution in the parasite Trichomonas vaginalis.

Cell Microbiol 2015 Aug 16;17(8):1217-29. Epub 2015 Mar 16.

Laboratorio de Parásitos Anaerobios, Instituto de Investigaciones Biotecnológicas-Instituto Tecnologico Chascomús (IIB-INTECH), CONICET-UNSAM, Chascomus, B7130IWA, Argentina.

The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection. Here, we report the cellular analysis of T.vaginalis tetraspanin family (TvTSPs). This family of membrane proteins has been implicated in cell adhesion, migration and proliferation in vertebrates. We found that the expression of several members of the family is up-regulated upon contact with vaginal ectocervical cells. We demonstrate that most TvTSPs are localized on the surface and intracellular vesicles and that the C-terminal intracellular tails of surface TvTSPs are necessary for proper localization. Analyses of full-length TvTSP8 and a mutant that lacks the C-terminal tail indicates that surface-localized TvTSP8 is involved in parasite aggregation, suggesting a role for this protein in parasite : parasite interaction.
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http://dx.doi.org/10.1111/cmi.12431DOI Listing
August 2015