Molecular characterization of Trypanosoma cruzi DTUs of the triatomine species in a Chagas disease endemic area

ABSTRACTAcetylation of lysine is a major posttranslational modification of proteins and is catalyzed by lysine acetyltransferases, while lysine deacetylases remove acetyl groups. Among the deacetylases, the sirtuins are NAD+-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting the proliferation of tumor cells, in this study, we investigated the role of these inhibitors in the growth and differentiation ofTrypanosoma cruzi, the agent of Chagas disease. We found that the use of salermide during parasite infection prevented growth and initial multiplication after mammalian cell invasion byT. cruziat concentrations that did not affect host cell viability. In addition,in vivoinfection was partially controlled upon administration of salermide. There are two sirtuins inT. cruzi, TcSir2rp1 and TcSir2rp3. By using specific antibodies and cell lines overexpressing the tagged versions of these enzymes, we found that TcSir2rp1 is localized in the cytosol and TcSir2rp3 in the mitochondrion. TcSir2rp1 overexpression acts to impair parasite growth and differentiation, whereas the wild-type version of TcSir2rp3 and not an enzyme mutated in the active site improves both. The effects observed with TcSir2rp3 were fully reverted by adding salermide, which inhibited TcSir2rp3 expressed inEscherichia coliwith a 50% inhibitory concentration (IC50) ± standard error of 1 ± 0.5 μM. We concluded that sirtuin inhibitors targeting TcSir2rp3 could be used in Chagas disease chemotherapy.

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Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole

Experimental Parasitology ◽

10.1016/j.exppara.2014.11.007 ◽

2015 ◽

Vol 148 ◽

pp. 73-80 ◽

Cited By ~ 7

Author(s):

Juciane Vaz Rêgo ◽

Ana Paula Duarte ◽

Daniel Barbosa Liarte ◽

Francirlene de Carvalho Sousa ◽

Humberto Medeiros Barreto ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Molecular Characterization

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Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822011005000058 ◽

2011 ◽

Vol 44 (6) ◽

pp. 684-690 ◽

Cited By ~ 12

Author(s):

César Gómez-Hernández ◽

Karine Rezende-Oliveira ◽

Gabriel Antônio Nogueira Nascentes ◽

Lara Rocha Batista ◽

Henrique Borges Kappel ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Random Amplified Polymorphic Dna ◽

Geographic Origin ◽

Pcr Amplification ◽

Biological Characterization ◽

Long Time ◽

Intergenic Regions ◽

Mexican Strains

INTRODUCTION: For a long time, the importance of Chagas disease in Mexico, where many regarded it as an exotic malady, was questioned. Considering the great genetic diversity among isolates of Trypanosoma cruzi, the importance of this biological characterization, and the paucity of information on the clinical and biological aspects of Chagas disease in Mexico, this study aimed to identify the molecular and biological characterization of Trypanosoma cruzi isolates from different endemic areas of this country, especially of the State of Jalisco. METHODS: Eight Mexican Trypanosoma cruzi strains were biologically and genetically characterized (PCR specific for Trypanosoma cruzi, multiplex-PCR, amplification of space no transcript of the genes of the mini-exon, amplification of polymorphic regions of the mini-exon, classification by amplification of intergenic regions of the spliced leader genes, RAPD - (random amplified polymorphic DNA). RESULTS: Two profiles of parasitaemia were observed, patent (peak parasitaemia of 4.6×10(6) to 10(7) parasites/mL) and subpatent. In addition, all isolates were able to infect 100% of the animals. The isolates mainly displayed tropism for striated (cardiac and skeletal) muscle. PCR amplification of the mini-exon gene classified the eight strains as TcI. The RAPD technique revealed intraspecies variation among isolates, distinguishing strains isolated from humans and triatomines and according to geographic origin. CONCLUSIONS: The Mexican T. cruzi strains are myotrophic and belong to group TcI.

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Trypanosoma cruzi and experimental Chagas' disease: characterization of a stock isolated from a patient with associated digestive and cardiac form

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821993000100006 ◽

1993 ◽

Vol 26 (1) ◽

pp. 25-33 ◽

Cited By ~ 7

Author(s):

E.C. Oliveira ◽

M.M.A. Stefani ◽

A.O. Luquetti ◽

E.F. Vêncio ◽

M.A.R. Moreira ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Digestive Tract ◽

Chagas Disease ◽

Acute Phase ◽

Experimental Infection ◽

Post Infection ◽

Chronic Phase ◽

Igg Antibodies ◽

Histopathology Examination

A new Trypanosoma cruzi stock isolated from a patient in the chronic phase of Chagas' disease with the digestive and cardiac fortn of the disease was characterized by experimental infection in isogenic, susceptible, A/Sn strain mice. Parasitemia curves showed up to 1.7x10(6) parasites/ml and no mortality was observed up to 300 days post infection. Specific IgM was found in mice in the acute phase up to 40 days and also in the chronic phase. IgG antibodies yvere detected in the acute and chronic phase. Histopathology examination demonstrated myotropism to the digestive tract muscle layers and to the heart.

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Identification and molecular characterization of two novel Trypanosoma cruzi genes encoding polypeptides sharing sequence motifs found in proteins involved in RNA editing reactions

Gene ◽

10.1016/s0378-1119(00)00253-5 ◽

2000 ◽

Vol 253 (2) ◽

pp. 271-280 ◽

Cited By ~ 4

Author(s):

Ali Ouaissi ◽

Baptiste Vergnes ◽

Margarida Borges ◽

Eliane Guilvard

Keyword(s):

Trypanosoma Cruzi ◽

Molecular Characterization ◽

Rna Editing ◽

Sequence Motifs ◽

Genes Encoding

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Characterization of human infection by Leishmania spp. in the Northwest of Argentina: immune response, double infection with Trypanosoma cruzi and species of Leishmania involved

Parasitology ◽

10.1017/s0031182002002585 ◽

2003 ◽

Vol 126 (1) ◽

pp. 31-39 ◽

Cited By ~ 48

Author(s):

F. M. FRANK ◽

M. M. FERNÁNDEZ ◽

N. J. TARANTO ◽

S. P. CAJAL ◽

R. A. MARGNI ◽

...

Keyword(s):

Immune Response ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Human Infection ◽

Double Infection ◽

Strong Immune Response ◽

American Tegumentary Leishmaniasis ◽

Leishmania Spp ◽

Very High

The aims of this study were to characterize human American tegumentary leishmaniasis, which includes cutaneous, mucocutaneous and mucosal leishmaniasis, in Northwest Argentina, to determine the prevalence of double infection with Trypanosoma cruzi and to identify the species of Leishmania in this area. Most of the 330 leishmaniasis patients presented cutaneous ulcers (96·1%), 2·4% mucocutaneous and 1·5% the mucosal form (‘espundia’). The aetiological agents, determined by isoenzyme electrophoresis, were identified as Leishmania (Viannia) braziliensis in 16 out of 20 isolates and in the remaining 4 as Leishmania (Leishmania) amazonensis, the first ever-documented in Argentina. Sera analysed by ELISA and IFA using complex antigen from both T. cruzi and L. braziliensis showed a very high percentage of positives (66·3–78·2%). When antigens for specific diagnosis of Chagas' disease were used, 40·9% of the leishmaniasis patients were also found to be infected by T. cruzi. These results indicate that the strong immune response against T. cruzi gave no protection to Leishmania, in spite of the serological cross-reaction between these parasites. In addition, we showed that more than 40% of the patients would be misdiagnosed as chagasic if complex antigens, as epimastigotes or soluble fraction from epimastigotes, were used in IFA or ELISA. This is of paramount importance not only because patients' treatment would be associated to misdiagnosis but the fact that in many countries in Central and South America, a positive test for Chagas' disease means a rejection for those seeking employment.

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