title: Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host.
abstract: The trace element selenium is found in polypeptides as selenocysteine, the 21(st) amino acid that is co-translationally inserted into proteins at a UGA codon. In proteins, selenocysteine usually plays a role as an efficient redox catalyst. Trypanosomatids previously examined harbor a full set of genes encoding the machinery needed for selenocysteine biosynthesis and incorporation into three selenoproteins: SelK, SelT and, the parasite-specific, Seltryp. We investigated the selenoproteome of kinetoplastid species in recently sequenced genomes and assessed the in vivo relevance of selenoproteins for African trypanosomes. Database mining revealed that SelK, SelT and Seltryp genes are present in most kinetoplastids, including the free-living species Bodo saltans, and Seltryp was lost in the subgenus Viannia from the New World Leishmania. Homology and sinteny with bacterial sulfur dioxygenases and sulfur transferases suggest a putative role for Seltryp in sulfur metabolism. A Trypanosoma brucei selenocysteine synthase (SepSecS) null-mutant, in which selenoprotein synthesis is abolished, displayed similar sensitivity to oxidative stress induced by a short-term exposure to high concentrations of methylglyoxal or H2O2 to that of the parental wild-type cell line. Importantly, the infectivity of the SepSecS knockout cell line was not impaired when tested in a mouse infection model and compensatory effects via up-regulation of proteins involved in thiol-redox metabolism were not observed. Collectively, our data show that selenoproteins are not required for survival of African trypanosomes in a mammalian host and exclude a role for selenoproteins in parasite antioxidant defense and/or virulence. On this basis, selenoproteins can be disregarded as drug target candidates.
authors.affiliation: Redox Biology of Trypanosomes Laboratory, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bonilla
authors.affiliation: Redox Biology of Trypanosomes Laboratory, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Erika
authors.initials: E
authors.lastname: Krull
authors.affiliation: Molecular Human Genetics Laboratory, Institut Pasteur de Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Florencia
authors.initials: F
authors.lastname: Irigoín
authors.affiliation: Worm Biology Laboratory, Institut Pasteur de Montevideo, Uruguay; Cátedra de Inmunología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Montevideo, Uruguay. Electronic address: gsalin@fq.edu.uy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Salinas
authors.affiliation: Redox Biology of Trypanosomes Laboratory, Institut Pasteur de Montevideo, Uruguay. Electronic address: mcomini@pasteur.edu.uy.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Comini
mesh_terms: D000818:Animals; D057225:Data Mining; D030541:Databases, Genetic; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016830:Kinetoplastida / Q000145:classification / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D010802:Phylogeny; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology; D017279:Selenocysteine / Q000378:metabolism*; D051140:Selenoproteins / Q000172:deficiency / Q000235:genetics*; D014166:Transferases / Q000172:deficiency / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000145:classification / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000469:parasitology / Q000473:pathology
chemical_list: D020543:Proteome; D015800:Protozoan Proteins; D051140:Selenoproteins; D017279:Selenocysteine; D011765:Pyruvaldehyde; D006861:Hydrogen Peroxide; D014166:Transferases; C060600:selenium transferase
keywords: Infection; Selenocysteine; Selenocysteine synthase; Sulfur metabolism; Thiol