@article{fdi:010053856,
  title = {{T}he {L}eishmania nicotinamidase is essential for {NAD}(+) production and parasite proliferation},
  author = {{G}azanion, {E}lodie and {G}arcia, {D}eborah and {S}ilvestre, {R}. and {G}{\'e}rard, {C}. and {G}uichou, {J}. {F}. and {L}abesse, {G}. and {S}eveno, {M}artial and {C}ordeiro-{D}a-{S}ilva, {A}. and {O}uaissi, {A}. and {S}ereno, {D}enis and {V}ergnes, {B}aptiste},
  editor = {},
  language = {{ENG}},
  abstract = {{NAD}(+) is a central cofactor that plays important roles in cellular metabolism and energy production in all living cells. {G}enomics-based reconstruction of {NAD}(+) metabolism revealed that {L}eishmania protozoan parasites are {NAD}(+) auxotrophs. {C}onsequently, these parasites require assimilating {NAD}(+) precursors (nicotinamide, nicotinic acid, nicotinamide riboside) from their host environment to synthesize {NAD}(+) by a salvage pathway. {N}icotinamidase is a key enzyme of this salvage pathway that catalyses conversion of nicotinamide ({NA}m) to nicotinic acid ({N}a), and that is absent in higher eukaryotes. {W}e present here the biochemical and functional characterizations of the {L}eishmania infantum nicotinamidase ({L}i{PNC}1). {G}eneration of {L}ipnc1 null mutants leads to a decrease in {NAD}(+) content, associated with a metabolic shutdown-like phenotype with an extensive lag phase of growth. {B}oth phenotypes could be rescued by an add-back construct or by addition of exogenous {N}a. {I}n addition, {L}ipnc1 null mutants were unable to establish a sustained infection in a murine experimental model. {A}ltogether, these results illustrate that {NAD}(+) homeostasis is a fundamental component of {L}eishmania biology and virulence, and that {NA}m constitutes its main {NAD}(+) source in the mammalian host. {T}he crystal structure of {L}i{PNC}1 we solved allows now the design of rational inhibitors against this new promising therapeutic target.},
  keywords = {},
  booktitle = {},
  journal = {{M}olecular {M}icrobiology},
  volume = {82},
  numero = {1},
  pages = {21--38},
  ISSN = {0950-382{X}},
  year = {2011},
  DOI = {10.1111/j.1365-2958.2011.07799.x},
  URL = {https://www.documentation.ird.fr/hor/fdi:010053856},
}