Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity

PLoS Neglected Tropical Diseases
Joana FariaAnabela Cordeiro-da-Silva

Abstract

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasit...Continue Reading

References

Mar 1, 1992·Bioscience, Biotechnology, and Biochemistry·A SugiyamaJ Oda
Jul 1, 1987·Molecular and Cellular Biology·I L AndrulisP N Ray
Jul 1, 1980·European Journal of Biochemistry·F Ramos, J M Wiame
Sep 25, 1981·Nucleic Acids Research·M NakamuraM Takanami
Sep 1, 1982·Journal of Bacteriology·L J Reitzer, B Magasanik
Feb 1, 1995·Trends in Biochemical Sciences·M C PeitschJ L Sussman
Jun 1, 1993·Analytical Biochemistry·S ShengS M Schuster
Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A K CruzS M Beverley
Mar 27, 2003·Molecular Microbiology·Christopher M SassettiEric J Rubin
Jul 16, 2005·Science·Najib M El-SayedNeil Hall
Jul 16, 2005·Science·Alasdair C IvensPeter J Myler
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Dec 27, 2005·Antimicrobial Agents and Chemotherapy·Huiping Ren, Jun Liu
Feb 27, 2007·BMC Evolutionary Biology·Andrew P Jackson
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ricardo SilvestreAli Ouaissi
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Sep 18, 2007·Eukaryotic Cell·Maria Carolina S MoraesBeatriz A Castilho
Oct 13, 2007·Science·Sabeeha S MerchantArthur R Grossman
Oct 22, 2008·Nucleic Acids Research·Florian KieferTorsten Schwede
Nov 11, 2008·Cell Host & Microbe·Dirk HofreuterJorge E Galán
Mar 20, 2009·The Biochemical Journal·Roderick A M WilliamsGraham H Coombs
Apr 25, 2009·Acta Crystallographica. Section D, Biological Crystallography·Charles Simon Bond, Alexander Wolfgang Schüttelkopf
Nov 6, 2009·Journal of Biomedicine & Biotechnology·Helena C Maltezou
Nov 17, 2009·Nucleic Acids Research·Cristina AurrecoecheaHaiming Wang
Apr 7, 2010·Infection and Immunity·Damien LeducHilde de Reuse
Jul 8, 2010·Journal of Global Infectious Diseases·Lukasz Kedzierski
Oct 19, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T LahavP J Myler
Nov 19, 2010·PloS One·Claudia ScottiVanio Vannini
Feb 1, 2011·Plant Physiology and Biochemistry : PPB·Stephen M G DuffBrad Fabbri
Feb 26, 2011·Immunological Reviews·Evelyne MougneauNicolas Glaichenhaus
Mar 15, 2011·Microbiology and Immunology·Keigo ShibayamaYoshichika Arakawa
May 12, 2011·PloS One·Sara J C GoslineMichael Hallett
Feb 1, 2012·PLoS Neglected Tropical Diseases·Diana MoreiraRicardo Silvestre
Jan 1, 2003·The Arabidopsis Book·Gloria M Coruzzi
Mar 1, 2012·The Journal of Biological Chemistry·Zachary N WilsonPhillip A Yates

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Citations

May 28, 2016·Scientific Reports·Joana FariaAnabela Cordeiro-da-Silva
Mar 30, 2017·Microbial Pathogenesis·Vinay KumarSushma Singh

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Methods Mentioned

BETA
Protein Assay
PCR
size exclusion chromatography
gene knock-out
phosphotransferase
transfection
size
ion exchange chromatographies
Fluorescence

Software Mentioned

ALSCRIPT Calcons
ImageJ
PyMOL Molecular Graphics System
GraphPad Prism
PyMOL
Aline
CELLO
TargetP
Biorad iCycler iQ Optical System
MITOPROT

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