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Mantilla 2017 PLOS Pathog
Coupling states LEAK  + , OXPHOS  + , ET  + , ROUTINE  +
Has abstract Adaptation to different nutritional enviro
Adaptation to different nutritional environments is essential for life cycle completion by all ''Trypanosoma brucei'' sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of ''T. b. brucei'' uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in ''T. b. brucei'' by studying mitochondrial Δ1-pyrroline-5-carboxylate dehydrogenase (TbP5CDH), which catalyzes the irreversible conversion of gamma-glutamate semialdehyde (γGS) into L-glutamate and NADH. In addition, we provided evidence for the absence of a functional proline biosynthetic pathway. TbP5CDH expression is developmentally regulated in the insect stages of the parasite, but absent in bloodstream forms grown ''in vitro''. RNAi down-regulation of TbP5CDH severely affected the growth of procyclic trypanosomes ''in vitro'' in the absence of glucose, and altered the metabolic flux when proline was the sole carbon source. Furthermore, TbP5CDH knocked-down cells exhibited alterations in the mitochondrial inner membrane potential (ΔΨm), respiratory control ratio and ATP production. Also, changes in the proline-glutamate oxidative capacity slightly affected the surface expression of the major surface glycoprotein EP-procyclin. In the tsetse, TbP5CDH knocked-down cells were impaired and thus unable to colonize the fly's midgut, probably due to the lack of glucose between bloodmeals. Altogether, our data show that the regulated expression of the proline metabolism pathway in ''T. b. brucei'' allows this parasite to adapt to the nutritional environment of the tsetse midgut.
ritional environment of the tsetse midgut.  +
Has editor [[Kandolf G]]  +
Has info [ PMID: 28114403 Open Access]  +
Has title Mantilla BS, Marchese L, Casas-Sánchez A, Dyer NA, Ejeh N, Biran M, Bringaud F, Lehane MJ, Acosta-Serrano A, Silber AM (2017) Proline metabolism is essential for ''Trypanosoma brucei brucei'' survival in the tsetse vector. PLOS Pathog 13:e1006158.  +
Instrument and method Oxygraph-2k  +
Mammal and model Protists  +
MiP area Respiration  +
Pathways S  + , ROX  + , N  +
Preparation Permeabilized cells  + , Intact cells  +
Was published by MiPNetLab BR Sao Paulo Silber AM +
Was published in journal PLOS Pathog +
Was published in year 2017  +
Was written by Mantilla BS + , Marchese L + , Casas-Sanchez A + , Dyer NA + , Ejeh N + , Biran M + , Bringaud F + , Lehane MJ + , Acosta-Serrano A + , Silber AM +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:09:18, 29 November 2017  +
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