Centro de Altos Estudios en Ciencias Humanas y de la Salud

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Browsing Centro de Altos Estudios en Ciencias Humanas y de la Salud by Author "Bustos, Patricia L."
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    A functional analysis of the cyclophilin repertoire in the protozoan parasite Trypanosoma cruzi
    (MDPI, 2018-10-31) Fuchs, Alicia Graciela ; Perrone, Alina E ; Milduberger, Natalia A. ; Bustos, Patricia L. ; Bua, Jaqueline
    Trypanosoma cruzi is the etiological agent of Chagas disease. It affects eight million people worldwide and can be spread by several routes, such as vectorborne transmission in endemic areas and congenitally, and is also important in non-endemic regions such as the United States and Europe due to migration from Latin America. Cyclophilins (CyPs) are proteins with enzymatic peptidyl-prolyl isomerase activity (PPIase), essential for protein folding in vivo. Cyclosporin A (CsA) has a high binding affinity for CyPs and inhibits their PPIase activity. CsA has proved to be a parasiticidal drug on some protozoa, including T. cruzi. In this review, we describe the T. cruzi cyclophilin gene family, that comprises 15 paralogues. Among the proteins isolated by CsA-affinity chromatography, we found orthologues of mammalian CyPs. TcCyP19, as the human CyPA, is secreted to the extracellular environment by all parasite stages and could be part of a complex interplay involving the parasite and the host cell. TcCyP22, an orthologue of mitochondrial CyPD, is involved in the regulation of parasite cell death. Our findings on T. cruzi cyclophilins will allow further characterization of these processes, leading to new insights into the biology, the evolution of metabolic pathways, and novel targets for anti-T. cruzi contro
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    A homolog of cyclophilin D is expressed in Trypanosoma cruzi and is involved in the oxidative stress–damage response
    (Cell Death Differentiation Association (ADMC), 2017-2-6) Bustos, Patricia L. ; Volta, Viviana J. ; Perrone, Alina E ; Milduberger, Natalia A. ; Bua, Jaqueline
    Mitochondria have an important role in energy production, homeostasis and cell death. The opening of the mitochondrial permeability transition pore (mPTP) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin D (CyPD), a crucial component of this protein complex. In Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin A-dependent manner, a well-known cyclophilin inhibitor. In the present work, a mitochondrial parasite cyclophilin, named TcCyP22, which is homolog to the mammalian CyPD was identified. TcCyP22-overexpressing parasites showed an enhanced loss of mitochondrial membrane potential and loss of cell viability when exposed to a hydrogen peroxide stimulus compared with control parasites. Our results describe for the first time in a protozoan parasite that a mitochondrial cyclophilin is a component of the permeability transition pore and is involved in regulated cell death induced by oxidative stress
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    Circulating cytokine and chemokine profiles of trypanosoma cruzi-infected women during pregnancy and its association with congenital transmission
    (Infectious Diseases Society of America (IDSA), 2021-9-15) Volta, Viviana J. ; Bustos, Patricia L. ; González, Carolina ; Natale, María Ailen ; Perrone, Alina E ; Milduberger, Natalia A. ; Laucella, Susana A. ; Bua, Jacqueline
    Background. Trypanosoma cruzi, the causative agent of Chagas disease, can be transmitted to the offspring of infected women, which constitutes an epidemiologically significant parasite transmission route in nonendemic areas. It is relevant to evaluate differ entially expressed factors in T. cruzi-infected pregnant women as potential markers of Chagas congenital transmission. Methods. Circulating levels of 12 cytokines and chemokines were measured by enzyme-linked immunosorbent assay or cytometric bead array in T. cruzi-infected and uninfected pregnant women in their second trimester of pregnancy and control groups of T. cruzi-infected and uninfected nonpregnant women. Results. Trypanosoma cruzi-infected women showed a proinflammatory Th1-biased profile, with increased levels of tumor ne crosis factor (TNF)-a, interleukin (IL)-12p70, IL-15, and monokine induced by interferon-gamma (MIG). Uninfected pregnant women presented a biased response towards Th2/Th17/Treg profiles, with increased plasma levels of IL-5, IL-6, IL-1ß, IL-17A, and IL-10. Finally, we identified that high parasitemia together with low levels of TNF-a, IL-15, and IL-17, low TNF-a/IL-10 ratio, and high IL-12p70 levels are factors associated with an increased probability of Chagas congenital transmission. Conclusions. Trypanosoma cruzi-infected pregnant women who did not transmit the infection to their babies exhibited a dis tinct proinflammatory cytokine profile that might serve as a potential predictive marker of congenital transmission.
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    Improved immuno-detection of a low-abundance cyclophilin allows the confirmation of its expression in a protozoan parasite
    (Hilaris, 2015-10-6) Bustos, Patricia L. ; Perrone, Alina E ; Milduberger, Natalia A. ; Bua, Jaqueline
    Protein samples can be challenging to analyze due to the presence of high-abundance proteins masking low abundance proteins of interest, such as biomarkers and novel physiological mediators. Cyclophilins are chaperones involved in the cis/trans isomerization of peptidyl-prolyl bonds in peptides or proteins and have been found in every organism sequenced to date. Although considerable progress has been made in the characterization of some cyclophilins expressed in diverse parasites invading humans, the main aspects of low-abundance members of this family remain unknown. In the present work, we present that the combined strategy of using more specific antibodies and increasing the presence of subcellular proteins in the sample, allowed us to confirm the expression of a 21.1 kDa cyclophilin for the first time in Trypanosoma cruzi.
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    Trypanosoma cruzi infection at the maternal-fetal interface : implications of parasite load in the congenital transmission and challenges in the diagnosis of infected newborns
    (Frontiers, 2019-6-7) Bustos, Patricia L. ; Milduberger, Natalia A. ; Volta, Viviana J. ; Perrone, Alina E ; Laucella, Susana A. ; Bua, Jacqueline
    Trypanosoma cruzi is the protozoan unicellular parasite that causes Chagas disease. It can be transmitted from infected mothers to their babies via the connatal route, thus being able to perpetuate even in the absence of Triatomine insect vectors. Chagas disease was originally endemic in Central and South America, but migration of infected women of childbearing age has spread the T. cruzi congenital infection to non-endemic areas like North America, Europe, Japan, and Australia. Currently, 7 million people are affected by this infection worldwide. This review focuses on the relevance of the T. cruzi parasite levels in different aspects of the congenital T. cruzi infection such as the mother-to-child transmission rate, the maternal and fetal immune response, and its impact on the diagnosis of infected newborns. Improvements in detection of this parasite, with tools that can be easily adapted to be used in remote rural areas, will make the early diagnosis of infected children possible, allowing a prompt trypanocidal treatment and avoiding the current loss of opportunities for the diagnosis of 100% of T. cruzi congenitally infected infants