Trypanosoma cruzi: high ribosomal resistance to trichosanthin inactivation.
Trypanosoma cruzi is the parasite causing Chagas Disease. Several results already published suggest that T. cruzi ribosomes have remarkable differences with their mammalian counterparts. In the present work, we showed that trypanosomatid (T. cruzi and Crithidia fasciculata) ribosomes are highly resistant to inactivation by trichosanthin (TCS), which is active against mammalian ribosomes. Differential resistance is an intrinsic feature of the ribosomal particles, as demonstrated by using assays where the only variable was the ribosomes source. Because we have recently described that TCS interacts with the acidic C-terminal end of mammalian ribosomal P proteins, we assayed the effect of a TCS variant, which is unable to interact with P proteins, on trypanosomatid ribosomes. This mutant showed similar shifting of IC(50) values on rat, T. cruzi and C. fasciculata ribosomes, suggesting that the resistance mechanism might involve other ribosomal components rather than the C-terminal end of P proteins.
Juri Ayub
Maximiliano
M
Fundación Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, 1405 Buenos Aires, Argentina. mayub@leloir.org.ar
Ma
Kit-Wan
KW
Shaw
Pang-Chui
PC
Wong
Kam-Bo
KB
D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D016831:Crithidia fasciculata / Q000187:drug effects / Q000648:ultrastructure; D004351:Drug Resistance; D008099:Liver / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D012270:Ribosomes / Q000187:drug effects*; D015978:Trichosanthin / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000648:ultrastructure
D000977:Antiparasitic Agents; D015978:Trichosanthin