@article{fdi:010036680,
  title = {{T}argeted disruption of cytosolic {SIR}2 deacetylase discloses its essential role in {L}eishmania survival and proliferation},
  author = {{V}ergnes, {B}aptiste and {S}ereno, {D}enis and {T}avares, {J}. and {C}ordeiro da {S}ilva, {A}. and {V}anhille, {L}. and {M}adjidian {S}ereno, {N}iloufar and {D}epoix, {D}. and {M}onte {A}legre, {A}draino and {O}uaissi, {A}li},
  editor = {},
  language = {{ENG}},
  abstract = {{P}roteins of the {SIR}2 family are characterized by a conserved catalytic domain that exerts unique {NAD}-dependent deacetylase activity on histone and various other cellular substrates. {F}unctional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any {SIR}2 genes. {H}ere using genetic approach, we report that a cytosolic {SIR}2 homolog in {L}eishmania is determinant to parasite survival. {L}. infantum promastigote tolerates deletion of one wild-type {L}i{SIR}2 allele ({L}i{SIR}2+/-) but achievement of null chromosomal mutants ({L}i{SIR}2-/-) requires episomal rescue. {A}ccordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. {T}hough single {L}i{SIR}2 gene disruption ({L}i{SIR}2+/-) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in {B}alb/c mice. {T}aken together these data support a stage specific requirement and/or activity of the {L}eishmania cytosolic {SIR}2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. {T}he lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes {L}i{SIR}2 protein a new attractive therapeutic target. (c) 2005 {E}lsevier {B}.{V}. {A}ll rights reserved.},
  keywords = {{L}eishmania infantum ; gene disruption ; {L}i{SIR}2 ; cell cycle ; virulence},
  booktitle = {},
  journal = {{G}ene},
  volume = {363},
  numero = {},
  pages = {85--96},
  ISSN = {0378-1119},
  year = {2005},
  DOI = {10.1016/j.gene.2005.06.047},
  URL = {https://www.documentation.ird.fr/hor/fdi:010036680},
}