Transcriptomic and proteomic analysis of quiescent epimastigotes as a resource for investigating Trypanosoma cruzi persistence.
Olmo, F.; Hesketh, A.; Hage, H.; Monneuse, J.-M.; Taylor, M. C.; Costa, F. C.; DaSilva, C.; Bequet, F.; Escudie, F.; Mercer, D.; Saliou, A.; Chatelain, E.; Kelly, J. M.; Abi Ghanem, J.
Show abstract
Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi. Despite triggering a strong immune response, infections are typically life-long and can result in severe cardiac and/or digestive tract pathology. Current drugs have limited efficacy, and treatment failure is a common outcome. Eliminating a non-replicating T. cruzi sub-population that can persist after therapy has been a key challenge for the drug-development community. Here, we describe the transcriptome and proteome profiles of quiescent epimastigote forms of the parasite isolated from exponentially growing cultures on the basis of reduced turnover of transiently-induced red fluorescent protein. This quiescent sub-population was characterised by down-regulation of genes/proteins involved in translation, metabolism, mitochondrial function and DNA replication, and by up-regulation of proteins that promote exit from the cell-cycle in other organisms. These data represent a resource that can be exploited to dissect the mechanistic basis of quiescence and to refine the drug-development screening cascade.
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