title: Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild-type and arginase-knockout mutants under arginine starvation.
abstract: l-Arginine is an essential amino acid in Leishmania (Leishmania) amazonensis metabolism. A key enzyme for parasite l-arginine metabolism is arginase (ARG) that uses arginine to produce urea and ornithine, a precursor of polyamine pathway guaranteeing parasite replication in both insect and mammal hosts. There is an alternative pathway to produce ornithine via l-proline and glutamate, but this mechanism is not described in Leishmania. In the mammal host, two enzymes can use l-arginine as substrate, the host ARG and the induced nitric oxide synthase that produces nitric oxide. The competition between induced nitric oxide synthase and both parasite and host ARG can favor the success of the infection or its control. Here, we established the metabolomics profile of the polyamine pathway of wild type (WT) L. (L.) amazonensis, submitted or not to l-arginine starvation, and compared to the ARG-knockout mutant (arg-). Our results indicated that arginine starvation induces a decrease in arginine, ornithine, and putrescine, but we could not detect the significative level changes of spermidine, spermine, or agmatine. However, the absence of ARG on the arg-induced an increase of arginine and citrulline levels, but decreased the levels of ornithine and putrescine. Similarly to the WT arginine-starved parasites, the arg-parasites presented lower levels of proline when compared to the WT ones. This could be indicative of an alternative pathway to surpass the enzyme or its substrate absence.
authors.affiliation: Colegiado de Medicina and Mestrado em Ciências da Saúde, Universidade Federal do Amapá, Amapá, Brazil.|Centro de Metabolómica y Bioanálisis (CEMBIO), Interacciones y Bioanálisis (UMIB), Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Emerson A
authors.initials: EA
authors.lastname: Castilho-Martins
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Interacciones y Bioanálisis (UMIB), Universidad CEU San Pablo, Madrid, Spain.|Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Gisele A B
authors.initials: GAB
authors.lastname: Canuto
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Sandra Marcia
authors.initials: SM
authors.lastname: Muxel
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Fernanda Laranjeira
authors.initials: MFL
authors.lastname: daSilva
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lucile Maria
authors.initials: LM
authors.lastname: Floeter-Winter
authors.affiliation: Departamento de Parasitologia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Del Aguila
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Interacciones y Bioanálisis (UMIB), Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: López-Gonzálvez
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Interacciones y Bioanálisis (UMIB), Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
keywords: Arginase; Arginine; Capillary eletrophoresis-mass spectrometry; Leishmania (Leishmania) amazonensis; Metabolomics