Cytosolic Fe-superoxide dismutase protects Trypanosoma cruzi from macrophage-derived superoxide radical increasing pathogen virulence in vivo

Martínez, Alejandra; Prolo, Carolina; Estrada, Damián; Ríos, Natalia; Piñeyro, Dolores; Robello, Carlos; Radí, Rafael; Piacenza, Lucı́a

doi:10.1016/j.freeradbiomed.2018.04.309

Cited by 5 publications

(8 citation statements)

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“…In view of the demonstration that the nude mitochondrion kDNA minicircle sequences cannot integrate in the macrophage genome, and of the infection stress-induced growth of the host and of the parasite eukaryotic cells [53,[105][106][107][108][109][110], we decided to test an array of drug inhibitors of metabolic pathways checkpoints. The optimal concentration of each of 12 drug inhibitors was tested in vitro against the T. cruzi forms.…”

Section: Discussionmentioning

confidence: 99%

“…Upon entry of T. cruzi into the body of the mammalian, the infective trypomastigotes are taken up by mononuclear phagocytes [52,[106][107][108][109][110]. The few intruding flagellate may be destroyed in the phagocytes, but the infection with many of the parasite replicate as amastigotes before returning to the trypomastigote forms that then burst out of the host cell to invade any tissue or cell type.…”

Section: Genetic Markers Of the Trypanosoma Cruzi Infectionmentioning

confidence: 99%

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The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Teixeira

Sousa

Gomes

et al. 2021

Preprint

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BackgroundThe Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease.MethodologyThe PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A target- primer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice.Principal findingsThe Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells.Conclusion and significanceThe T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.Authors summaryChagas disease is considered the main cause of human heart failure in the Western Hemisphere. The treatment of the clinically manifested Chagas heart disease is considered unsatisfactory. Perhaps the most important problem in the field of Chagas disease is determination of the pathogenesis of the target heart cells lysis. We showed the transfer of the T. cruzi kDNA minicircle sequences into the genome of rabbits and mice, and to Bird refractory to the infections. The inoculation of a few T. cruzi in the fertile chicken eggs renders the kDNA sequences integration in the stem cells. Interestingly, the chicks that hatched retain the kDNA and develop the Chagas-like cardiomyopathy indistinguishable to that in the rabbits and mice. This result prompted the multidrug treatment of the Chagas heart disease with inhibitors of the eukaryotic cells division. We showed that nine out of 12 inhibitors prevented the transfer of the kDNA mutations into the macrophage genome, and that the treatment of the acutely T. cruzi-infected mice with Benznidazole + Ofloxacin + Azidothymidine lowered circa 2.5-fold the rate of the mutations in the chromosomes. These findings translated to the pathology showing inhibition of the heart lesions in the treated T. cruzi-infected mice. We suggest purposing new inhibitors should be tested to overturning the Chagas heart disease.

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Markers Of the Trypanosoma Cruzi Infectionmentioning

confidence: 99%

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Teixeira

Sousa

Gomes

et al. 2021

Preprint

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“…Através do exame de Fixação de Complemento, um estudo mostrou que das 68 casas de campo, onde as amostras coletadas de cães e gatos foram conclusivas, 32, 35% , ou seja, pelo menos um animal estava infectado com T. cruzi em 22 dessas casas 29 .…”

Section: Diagnósticounclassified

Saúde Pública No Século Xxi: Uma Abordagem Multidisciplinar

Silva,

Oliveira,

Nascimento

et al. 2024

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Hoje o mundo passa por várias crises de saúde pública, quais são os problemas globais? Quais são as verdadeiras pandemias que estamos enfrentando neste século? O que temos a nossa frente e qual a importância da Atenção Primária a Saúde no combate destas enfermidades? Para tentar responder a estas questões foi feita uma revisão de artigos científicos, e feita uma busca em bases oficiais de dados epidemiológicos, onde se constatou que os grandes desafios do nosso século não são mais as doenças infecciosas e parasitárias, mas as doenças crônicas não transmissíveis, pois passamos por um processo de transição epidemiológica que mudou as causas de morte da população do Brasil e do mundo, nosso grande desafio hoje é combater a diabetes, hipertensão e obesidade, doenças que matam mais que qualquer patógeno conhecido. A grande mudança que se deve promover é uma mudança de estilo de vida, com melhores hábitos alimentares e atividade física. A promoção da Saúde e o acompanhamento e tratamento destas doenças crônicas por parte da Atenção Primária a Saúde é o caminho para mudar e reverter este quadro em que nos encontramos hoje. Precisamos combater as grandes pandemias do nosso século, assim combatemos as duas maiores causas de morte segundo a Organização Mundial de Saúde, a Cardiopatia Isquêmica e o Acidente Vascular Cerebral.

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“…An Fe-SOD enriched T. cruzi showed an almost two-fold rate of survival compared to the WT when challenged with macrophages [ 84 ]. Fe-SODB can detoxify cytosolic superoxide derived from macrophages, preventing damage and increasing the virulence of T. cruzi [ 89 ].…”

Section: Protistsmentioning

confidence: 99%

Superoxide Dismutases in Eukaryotic Microorganisms: Four Case Studies

Valle

Scheckhuber

2022

Antioxidants

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Various components in the cell are responsible for maintaining physiological levels of reactive oxygen species (ROS). Several different enzymes exist that can convert or degrade ROS; among them are the superoxide dismutases (SODs). If left unchecked, ROS can cause damage that leads to pathology, can contribute to aging, and may, ultimately, cause death. SODs are responsible for converting superoxide anions to hydrogen peroxide by dismutation. Here we review the role of different SODs on the development and pathogenicity of various eukaryotic microorganisms relevant to human health. These include the fungal aging model, Podospora anserina; various members of the genus Aspergillus that can potentially cause aspergillosis; the agents of diseases such as Chagas and sleeping disease, Trypanosoma cruzi and Trypanosoma brucei, respectively; and, finally, pathogenic amoebae, such as Acanthamoeba spp. In these organisms, SODs fulfill essential and often regulatory functions that come into play during processes such as the development, host infection, propagation, and control of gene expression. We explore the contribution of SODs and their related factors in these microorganisms, which have an established role in health and disease.

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Cytosolic Fe-superoxide dismutase protects Trypanosoma cruzi from macrophage-derived superoxide radical increasing pathogen virulence in vivo

Cited by 5 publications

References 0 publications

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Saúde Pública No Século Xxi: Uma Abordagem Multidisciplinar

Superoxide Dismutases in Eukaryotic Microorganisms: Four Case Studies

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