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Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs

Toxoplasma gondii is the causative agent of toxoplasmosis in animals and humans. This infection is transmitted to humans through oocysts released in the feces of the felines into the environment or by ingestion of undercooked meat. This implies that toxoplasmosis is a zoonotic disease and T. gondii...

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Autores principales: Angel, Sergio O., Vanagas, Laura, Ruiz, Diego M., Cristaldi, Constanza, Saldarriaga Cartagena, Ana M., Sullivan, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325978/
https://www.ncbi.nlm.nih.gov/pubmed/32656097
http://dx.doi.org/10.3389/fcimb.2020.00289
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author Angel, Sergio O.
Vanagas, Laura
Ruiz, Diego M.
Cristaldi, Constanza
Saldarriaga Cartagena, Ana M.
Sullivan, William J.
author_facet Angel, Sergio O.
Vanagas, Laura
Ruiz, Diego M.
Cristaldi, Constanza
Saldarriaga Cartagena, Ana M.
Sullivan, William J.
author_sort Angel, Sergio O.
collection PubMed
description Toxoplasma gondii is the causative agent of toxoplasmosis in animals and humans. This infection is transmitted to humans through oocysts released in the feces of the felines into the environment or by ingestion of undercooked meat. This implies that toxoplasmosis is a zoonotic disease and T. gondii is a foodborne pathogen. In addition, chronic toxoplasmosis in goats and sheep is the cause of recurrent abortions with economic losses in the sector. It is also a health problem in pets such as cats and dogs. Although there are therapies against this infection in its acute stage, they are not able to permanently eliminate the parasite and sometimes they are not well tolerated. To develop better, safer drugs, we need to elucidate key aspects of the biology of T. gondii. In this review, we will discuss the importance of the homologous recombination repair (HRR) pathway in the parasite's lytic cycle and how components of these processes can be potential molecular targets for new drug development programs. In that sense, the effect of different DNA damage agents or HHR inhibitors on the growth and replication of T. gondii will be described. Multitarget drugs that were either associated with other targets or were part of general screenings are included in the list, providing a thorough revision of the drugs that can be tested in other scenarios.
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spelling pubmed-73259782020-07-09 Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs Angel, Sergio O. Vanagas, Laura Ruiz, Diego M. Cristaldi, Constanza Saldarriaga Cartagena, Ana M. Sullivan, William J. Front Cell Infect Microbiol Cellular and Infection Microbiology Toxoplasma gondii is the causative agent of toxoplasmosis in animals and humans. This infection is transmitted to humans through oocysts released in the feces of the felines into the environment or by ingestion of undercooked meat. This implies that toxoplasmosis is a zoonotic disease and T. gondii is a foodborne pathogen. In addition, chronic toxoplasmosis in goats and sheep is the cause of recurrent abortions with economic losses in the sector. It is also a health problem in pets such as cats and dogs. Although there are therapies against this infection in its acute stage, they are not able to permanently eliminate the parasite and sometimes they are not well tolerated. To develop better, safer drugs, we need to elucidate key aspects of the biology of T. gondii. In this review, we will discuss the importance of the homologous recombination repair (HRR) pathway in the parasite's lytic cycle and how components of these processes can be potential molecular targets for new drug development programs. In that sense, the effect of different DNA damage agents or HHR inhibitors on the growth and replication of T. gondii will be described. Multitarget drugs that were either associated with other targets or were part of general screenings are included in the list, providing a thorough revision of the drugs that can be tested in other scenarios. Frontiers Media S.A. 2020-06-12 /pmc/articles/PMC7325978/ /pubmed/32656097 http://dx.doi.org/10.3389/fcimb.2020.00289 Text en Copyright © 2020 Angel, Vanagas, Ruiz, Cristaldi, Saldarriaga Cartagena and Sullivan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Angel, Sergio O.
Vanagas, Laura
Ruiz, Diego M.
Cristaldi, Constanza
Saldarriaga Cartagena, Ana M.
Sullivan, William J.
Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title_full Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title_fullStr Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title_full_unstemmed Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title_short Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs
title_sort emerging therapeutic targets against toxoplasma gondii: update on dna repair response inhibitors and genotoxic drugs
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325978/
https://www.ncbi.nlm.nih.gov/pubmed/32656097
http://dx.doi.org/10.3389/fcimb.2020.00289
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