Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

Abràs, Alba; Ballart, Cristina; Fernández-Arévalo, Anna; Pinazo, María Jesús; Gascón, Joaquím; Muñoz, Carmen; Gállego, Montserrat

doi:10.1128/cmr.00152-21

Cited by 44 publications

(51 citation statements)

References 218 publications

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“…Chagas disease has spread all over the world due to migration, which has brought the disease outside of the endemic areas and the transmission occurs vertically (congenital) and via blood and tissue/organ donations [ 2 , 4 ]. In endemic areas, the disease is transmitted by blood-sucking insects of the subfamily Triatominae, which can infect a mammalian host [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)

Maldonado

Rojas²,

Urbina³

et al. 2022

Cells

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DNA polymerase β plays a fundamental role in the life cycle of Trypanosoma cruzi since it participates in the kinetoplast DNA repair and replication. This enzyme can be found in two forms in cell extracts of T. cruzi epimastigotes form. The H form is a phosphorylated form of DNA polymerase β, while the L form is not phosphorylated. The protein kinases which are able to in vivo phosphorylate DNA polymerase β have not been identified yet. In this work, we purified the H form of this DNA polymerase and identified the phosphorylation sites. DNA polymerase β is in vivo phosphorylated at several amino acid residues including Tyr35, Thr123, Thr137 and Ser286. Thr123 is phosphorylated by casein kinase 2 and Thr137 and Ser286 are phosphorylated by protein kinase C-like enzymes. Protein kinase C encoding genes were identified in T. cruzi, and those genes were cloned, expressed in bacteria and the recombinant protein was purified. It was found that T. cruzi possesses three different protein kinase C-like enzymes named TcPKC1, TcPKC2, and TcPKC3. Both TcPKC1 and TcPKC2 were able to in vitro phosphorylate recombinant DNA polymerase β, and in addition, TcPKC1 gets auto phosphorylated. Those proteins contain several regulatory domains at the N-terminus, which are predicted to bind phosphoinositols, and TcPKC1 contains a lipocalin domain at the C-terminus that might be able to bind free fatty acids. Tyr35 is phosphorylated by an unidentified protein kinase and considering that the T. cruzi genome does not contain Tyr kinase encoding genes, it is probable that Tyr35 could be phosphorylated by a dual protein kinase. Wee1 is a eukaryotic dual protein kinase involved in cell cycle regulation. We identified a Wee1 homolog in T. cruzi and the recombinant kinase was assayed using DNA polymerase β as a substrate. T. cruzi Wee1 was able to in vitro phosphorylate recombinant DNA polymerase β, although we were not able to demonstrate specific phosphorylation on Tyr35. Those results indicate that there exists a cell signaling pathway involving PKC-like kinases in T. cruzi.

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Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)

Maldonado

Rojas²,

Urbina³

et al. 2022

Cells

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“…Chagas disease is primarily found in endemic areas of 21 countries in the Latin American continent and is mostly transmitted to humans through contact with the feces or urine of triatomine bugs (vector-borne) [69]. Although the majority of these infected individuals reside in Mexico, Central America, and South America, migration patterns have resulted in large numbers of infected individuals in formerly nonaffected areas, including Europe, Japan, Australia, Canada, and the United States [70], with an estimated 300,000 individuals in the United States alone [71]. These bed bugs are also known as "kissing bugs" and have many other names depending on the geographic area.…”

Section: Trypanosoma Cruzi Infection-induced Cardiomyopathymentioning

confidence: 99%

“…In Latin America, Trigonoscuta cruzi is mainly transmitted by contact with the feces/ urine of infected blood-sucking Triton bugs. These parasite-carrying insects typically live in cracks in the walls or roofs of rural or suburban houses and surrounding structures such as chicken coops, pens and warehouses [71]. Normally, they hide during the day and become active at night, feeding on blood from animals, including humans.…”

Section: Transmissionmentioning

confidence: 99%

Stress-Induced Cardiomyopathy

Wen¹,

Radhakrishnan²

2023

Novel Pathogenesis and Treatments for Cardiovascular Disease

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The irreversible termination of individual life activities and metabolism means all fatal problems ultimately terminate the heart function. It’s very important to protect the patient’s life if we have treatment to maintain heart function and care about patients’ heart response. It is known that many diseases induced heart dysfunction including Chagas disease, burn injury, smoking and other bad stresses. Chronic stress causes these physical symptoms and emotional symptoms. Due to the awareness created by the media and internet, patients are generally aware that they should seek help immediately for chest pain. Therefore, attention and studies on stress-induced heart dysfunction would help uncover the pathophysiological mechanisms of cardiac response to non-heart diseases and provide an insight of heart-protection drugs. At the same time, physicians should be aware of this new condition and how to diagnose and treat it, even though the causal mechanisms are not yet fully understood. This special chapter will discuss on the cardiac response to the stresses especially on our associated research in recent decades such as Trypanosoma cruzi (T. cruzi)-induced cardiomyopathy and burn injury–induced cardiomyopathy, and on some very popular stresses such as behavior, motion, mental, and smoking.

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“…In Spain, both transfusion and transplant transmission are routes that are rigorously controlled by the serological screening of donors and the close monitoring of recipients of organs from chagasic donors ( 3 , 4 ); therefore, the mother-to-child route is the main mode of transmission contributing to autochthonous CD. Although there is as yet no official management plan at the national level ( 5 ), serological screening in pregnant women is performed in most hospitals. In areas where the disease is not endemic, vertical transmission is the leading cause of episodes equivalent to acute infection if CD is confirmed in the first months of a child’s life.…”

Section: Introductionmentioning

confidence: 99%

Parasitemia Levels in Trypanosoma cruzi Infection in Spain, an Area Where the Disease Is Not Endemic: Trends by Different Molecular Approaches

et al. 2022

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Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

Cited by 44 publications

References 218 publications

Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)

Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)

Stress-Induced Cardiomyopathy

Parasitemia Levels in Trypanosoma cruzi Infection in Spain, an Area Where the Disease Is Not Endemic: Trends by Different Molecular Approaches

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