Genomics-driven reconstruction of acinetobacter NAD metabolism: insights for antibacterial target selection.

The Journal of Biological Chemistry
Leonardo SorciAndrei Osterman

Abstract

Enzymes involved in the last steps of NAD biogenesis, nicotinate mononucleotide adenylyltransferase (NadD) and NAD synthetase (NadE), are conserved and essential in most bacterial species and are established targets for antibacterial drug development. Our genomics-based reconstruction of NAD metabolism in the emerging pathogen Acinetobacter baumannii revealed unique features suggesting an alternative targeting strategy. Indeed, genomes of all analyzed Acinetobacter species do not encode NadD, which is functionally replaced by its distant homolog NadM. We combined bioinformatics with genetic and biochemical techniques to elucidate this and other important features of Acinetobacter NAD metabolism using a model (nonpathogenic) strain Acinetobacter baylyi sp. ADP1. Thus, a comparative kinetic characterization of PncA, PncB, and NadV enzymes allowed us to suggest distinct physiological roles for the two alternative, deamidating and nondeamidating, routes of nicotinamide salvage/recycling. The role of the NiaP transporter in both nicotinate and nicotinamide salvage was confirmed. The nondeamidating route was shown to be transcriptionally regulated by an ADP-ribose-responsive repressor NrtR. The NadM enzyme was shown to possess dual s...Continue Reading

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Citations

Apr 30, 2013·Briefings in Functional Genomics·Bas E DutilhSacha A F T van Hijum
Dec 4, 2012·Journal of Bacteriology·Leonardo SorciAndrei L Osterman
Jun 22, 2012·PloS One·Jessica De IngeniisLeonardo Sorci
Jun 1, 2013·PloS One·João CarneiroRaquel M Silva
Oct 29, 2011·IUBMB Life·Kathryn T Elliott, Ellen L Neidle
Aug 17, 2014·DNA Repair·Leonardo SorciNadia Raffaelli
May 20, 2014·Biochimica Et Biophysica Acta·Michael Jaehme, Dirk Jan Slotboom
Oct 27, 2016·Molecular Microbiology·Timothy J BrickmanSandra K Armstrong
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Jan 30, 2015·The Journal of Biological Chemistry·Irina A RodionovaAndrei L Osterman
Jul 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Mathias BockwoldtInes Heiland
Feb 16, 2021·Frontiers in Microbiology·Kyle H Rohde, Leonardo Sorci

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