Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis in Trypanosoma cruzi

Author(s)

Oliveira Souza, Rodolpho Ornitz ^[1] ; Crispim, Marcell ^[1] ; Silber, Ariel Mariano ^[1] ; Damasceno, Flavia Silva ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Biochem Tryps LaBTryps, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecules; v. 25, n. 7 APR 2020.
• Web of Science Citations: 0

Abstract

Trypanosoma cruzi is the aetiologic agent of Chagas disease, which affects people in the Americas and worldwide. The parasite has a complex life cycle that alternates among mammalian hosts and insect vectors. During its life cycle, T. cruzi passes through different environments and faces nutrient shortages. It has been established that amino acids, such as proline, histidine, alanine, and glutamate, are crucial to T. cruzi survival. Recently, we described that T. cruzi can biosynthesize glutamine from glutamate and/or obtain it from the extracellular environment, and the role of glutamine in energetic metabolism and metacyclogenesis was demonstrated. In this study, we analysed the effect of glutamine analogues on the parasite life cycle. Here, we show that glutamine analogues impair cell proliferation, the developmental cycle during the infection of mammalian host cells and metacyclogenesis. Taken together, these results show that glutamine is an important metabolite for T. cruzi survival and suggest that glutamine analogues can be used as scaffolds for the development of new trypanocidal drugs. These data also reinforce the supposition that glutamine metabolism is an unexplored possible therapeutic target. (AU)

• FAPESP's process: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi
• Grantee: Ariel Mariano Silber
• Support Opportunities: Research Projects - Thematic Grants