Life Cycle of Pathogenic Protists: Trypanosoma cruzi

Barrias, Emile; Zuma, Aline Araújo; Souza, Wanderley de

doi:10.1007/978-3-030-80682-8_1

Cited by 1 publication

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“…In endemic areas, the disease is transmitted by blood-sucking insects of the subfamily Triatominae, which can infect a mammalian host [ 5 ]. The T. cruzi parasite is an intracellular protozoan that can undergo a complex life cycle between the insect vector and a mammalian host [ 5 , 6 , 7 ]. The parasite adopts four main forms during its life cycle: two in the insect vector, which are epimastigotes (replicative form) and metacyclic trypomastigotes (non-replicative and infectious form) [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The T. cruzi parasite is an intracellular protozoan that can undergo a complex life cycle between the insect vector and a mammalian host [ 5 , 6 , 7 ]. The parasite adopts four main forms during its life cycle: two in the insect vector, which are epimastigotes (replicative form) and metacyclic trypomastigotes (non-replicative and infectious form) [ 5 , 6 , 7 ]. The mammalian host also adopts two forms, amastigote (replicative intracellular form) and blood trypomastigote (non-replicative form) [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The parasite adopts four main forms during its life cycle: two in the insect vector, which are epimastigotes (replicative form) and metacyclic trypomastigotes (non-replicative and infectious form) [ 5 , 6 , 7 ]. The mammalian host also adopts two forms, amastigote (replicative intracellular form) and blood trypomastigote (non-replicative form) [ 5 , 6 , 7 ]. During this digenetic life cycle, the parasite faces a variety of changes in environmental conditions, and it must quickly adapt in order to survive and proliferate.…”

Section: Introductionmentioning

confidence: 99%

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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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