Exploring protein myristoylation in Toxoplasma gondii

ANDRÉS ALONSO; VALERIA R TUROWSKY; DIEGO M RUIZ; BARBARA ORELO; JAMES MORESCO; JHON YATES; MARIA CORVI

EXPERIMENTAL PARASITOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2019

0014-4894

Toxoplasma gondii is an important human and veterinary pathogen and thecausative agent of toxoplasmosis, a potentially severe disease especially inimmunocompromisedorcongenitallyinfectedhumans.Currenttherapeuticcompounds are not well-tolerated, present increasing resistance, limited efficacy andrequire long periods of treatment. On this context, searching for new therapeutictargets is crucial to drug discovery. In this sense, recent works suggest that N-myristoyltransferase (NMT), the enzyme responsible for protein myristoylation that isessential in some parasites, could be the target of new anti-parasitic compounds.However, up to date there is no information on NMT and the extent of thismodification in T. gondii. In this work, we decided to explore T. gondii genome insearch of elements related with the N-myristoylation process. By a bioinformaticsapproach it was possible to identify a putative T. gondii NMT (TgNMT). This enzymethat is homologous to other parasitic NMTs, presents activity in vitro, is expressed inboth intra- and extracellular parasites and interacts with predicted TgNMTsubstrates. Additionally, NMT activity seems to be important for the lytic cycle ofToxoplasma gondii. In parallel, an in silico myristoylome predicts 157 proteins to beaffected by this modification. Myristoylated proteins would be affecting severalmetabolic functions with some of them being critical for the life cycle of this parasite.Together, these data indicate that TgNMT could be an interesting target ofintervention for the treatment of toxoplasmosis.