Trypanosoma cruzi: Characterisation of the gene encoding tyrosine aminotransferase in benznidazole-resistant and susceptible populations

Various biochemical differences exist between mammalian tyrosine aminotransfierase (TAT) and its analogue in Trypanosoma cruzi (TcTAT), the causative agent of Chagas disease. Moreover, TcTAT is over-expressed in strains of the parasite that are resistant to benznidazole (BZ), a drug currently used in chemotherapy. TAT has thus been indicated as a potential target for the development of new chemotherapeutic agents. In the present study, the TcTAT gene has been characterised in 14 BZ-resistant and susceptible strains and clones of T cruzi. A unique transcript of 2.0 kb and similar levels of TcTAT mRNA were observed in all parasite populations. TcTAT gene is organized in a tandem multicopy array and is located on 8 chromosomal bands that vary from 785-2500 kb. No amplification of TcTAT was observed in the parasite genome. A 42 kDa protein expressed by TcTAT was present in all T cruzi samples. The results suggest that TcTAT is not directly associated with the T cruzi drug resistance phenotype. However, it may act as a general secondary compensatory mechanism or stress response factor rather than as a key component of the specific primary resistance mechanism in T cruzi. (c) 2007 Published by Elsevier Inc.