The Leishmania nicotinamidase is essential for NAD+ production and parasite proliferation

Molecular Microbiology
Elodie GazanionBaptiste Vergnes


NAD+ is a central cofactor that plays important roles in cellular metabolism and energy production in all living cells. Genomics-based reconstruction of NAD+ metabolism revealed that Leishmania protozoan parasites are NAD+ auxotrophs. Consequently, these parasites require assimilating NAD+ precursors (nicotinamide, nicotinic acid, nicotinamide riboside) from their host environment to synthesize NAD+ by a salvage pathway. Nicotinamidase is a key enzyme of this salvage pathway that catalyses conversion of nicotinamide (NAm) to nicotinic acid (Na), and that is absent in higher eukaryotes. We present here the biochemical and functional characterizations of the Leishmania infantum nicotinamidase (LiPNC1). Generation of Lipnc1 null mutants leads to a decrease in NAD+ content, associated with a metabolic shutdown-like phenotype with an extensive lag phase of growth. Both phenotypes could be rescued by an add-back construct or by addition of exogenous Na. In addition, Lipnc1 null mutants were unable to establish a sustained infection in a murine experimental model. Altogether, these results illustrate that NAD+ homeostasis is a fundamental component of Leishmania biology and virulence, and that NAm constitutes its main NAD+ source in t...Continue Reading


Sep 22, 2001·International Journal for Parasitology·R J Burchmore, M P Barrett
Mar 22, 2003·Current Opinion in Cell Biology·Su-Ju Lin, Leonard Guarente
Jun 20, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Anthony RongvauxOberdan Leo
Jun 25, 2003·Current Opinion in Infectious Diseases·Shyam Sundar, Madhukar Rai
Jan 20, 2004·Molecular and Cellular Biology·Christopher M GalloJeffrey S Smith
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 9, 2004·The Biochemical Journal·Mathias Ziegler, Marc Niere
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 28, 2005·Antimicrobial Agents and Chemotherapy·Denis SerenoAli Ouaissi
Mar 19, 2005·Science·Renee DomergueBrendan P Cormack
Jul 16, 2005·Science·Alasdair C IvensPeter J Myler
Mar 27, 2007·Archives of Biochemistry and Biophysics·Gang HuP John Hart
May 12, 2007·International Journal for Parasitology·Sébastien BesteiroJeremy C Mottram
Jun 19, 2007·International Journal for Parasitology·Gabriela Cohen-FreueW Robert McMaster
Jun 26, 2007·Journal of Bacteriology·Anne-Laure PrunierAnthony T Maurelli
Jul 4, 2007·Trends in Parasitology·Malcolm J McConvilleThomas Naderer
Aug 30, 2007·Molecular Microbiology·Biao MaBrendan P Cormack
Jan 19, 2008·The FEBS Journal·Hua ZhangXian-En Zhang
Feb 9, 2008·The Journal of Biological Chemistry·Peter A BelenkyCharles Brenner
Feb 17, 2009·Cell Host & Microbe·Kellen L OlszewskiManuel Llinás
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Mar 5, 2010·Molecular Microbiology·Catherine VilchèzeWilliam R Jacobs
Oct 1, 2010·Biochemistry·Derrick R SeinerJohn S Blanchard
Oct 5, 2010·Parasitology International·Elodie GazanionDenis Sereno


Mar 2, 2013·PloS One·Guiomar Sánchez-CarrónÁlvaro Sánchez-Ferrer
Jun 1, 2013·PloS One·João CarneiroRaquel M Silva
Apr 22, 2014·PloS One·Jessica K O'HaraManuel Llinás
Jul 5, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ifedayo Victor Ogungbe, William N Setzer
Jan 1, 2016·Cellular and Molecular Life Sciences : CMLS·Inês MesquitaRicardo Silvestre
Sep 1, 2015·Protein Expression and Purification·Luis E ContrerasMaría H Ramírez
Jan 28, 2014·Journal of Molecular Graphics & Modelling·Ifedayo Victor OgungbeWilliam N Setzer
Apr 29, 2015·BioMed Research International·Lourival A SilvaJosé Clecildo B Bezerra
Feb 1, 2012·PLoS Neglected Tropical Diseases·Diana MoreiraRicardo Silvestre
Jun 15, 2016·Molecular and Biochemical Parasitology·Baptiste VergnesThomas Grentzinger
May 28, 2011·International Immunopharmacology·Rajeev Nagill, Sukhbir Kaur
Oct 25, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ifedayo Victor Ogungbe, William N Setzer
May 3, 2018·Expert Opinion on Therapeutic Targets·Shyam Sundar, Bhawana Singh
Jul 28, 2016·Applied and Environmental Microbiology·Xiaolan WangShengqing Yu
Dec 21, 2018·Microbiology and Molecular Biology Reviews : MMBR·Pamlea N BradyMargaret A Johnson
Aug 1, 2019·The Journal of Antimicrobial Chemotherapy·Baptiste VergnesAnne-Laure Bañuls
Jan 15, 2014·Organic & Biomolecular Chemistry·Xiang Sheng, Yongjun Liu
Dec 12, 2018·Journal of Biomolecular Structure & Dynamics·Haraprasad MandalPradeep Das
Mar 28, 2019·Memórias do Instituto Oswaldo Cruz·Lesly Ortiz-JoyaMaría Helena Ramírez-Hernández
Jul 18, 2015·Microbiology Spectrum·Arianna Corona, Ira Schwartz

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