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.

Frontiers in Cellular and Infection Microbiology

Frontiers Media S.A.

Año: 2020 vol. 10

Toxoplasmagondii is the causativeagent of toxoplasmosis in animals and humans. This infection is transmitted tohumans through oocysts released in the feces of the felines into theenvironment or by ingestion of undercooked meat. This implies thattoxoplasmosis is a zoonotic disease and T.gondii is a foodborne pathogen. In addition, chronic toxoplasmosis in goatsand sheep is the cause of recurrent abortions with economic losses in thesector. It is also a health problem in pets such as cats and dogs. Althoughthere are therapies against this infection in its acute stage, they are notable to permanently eliminate the parasite and sometimes they are not welltolerated. To develop better, safer drugs, we need to elucidate key aspects ofthe biology of T. gondii. In thisreview, we will discuss the importance of the homologous recombination repair(HRR) pathway in the parasite´s lytic cycle and how components of theseprocesses can be potential molecular targets for new drug development programs.In that sense, the effect of different DNA damage agents or HHR inhibitors onthe growth and replication of T. gondiiwill be described. Multitarget drugs that were either associated with othertargets or were part of general screenings are included in the list, providing athorough revision of the drugs that can be tested in other scenarios.