NADP and NAD utilization in Haemophilus influenzae
Article first published online: 18 JAN 2002
Volume 35, Issue 6, pages 1573–1581, March 2000
How to Cite
Reidl, J., Schlör, S., Kraiß, A., Schmidt-Brauns, J., Kemmer, G. and Soleva, E. (2000), NADP and NAD utilization in Haemophilus influenzae. Molecular Microbiology, 35: 1573–1581. doi: 10.1046/j.1365-2958.2000.01829.x
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Received 25 October, 1999; revised 30 December, 1999; accepted 5 January, 2000.
Exogenous NAD utilization or pyridine nucleotide cycle metabolism is used by many bacteria to maintain NAD turnover and to limit energy-dependent de novo NAD synthesis. The genus Haemophilus includes several important pathogenic bacterial species that require NAD as an essential growth factor. The molecular mechanisms of NAD uptake and processing are understood only in part for Haemophilus. In this report, we present data showing that the outer membrane lipoprotein e(P4), encoded by the hel gene, and an exported 5′-nucleotidase (HI0206), assigned as nadN, are necessary for NAD and NADP utilization. Lipoprotein e(P4) is characterized as an acid phosphatase that uses NADP as substrate. Its phosphatase activity is inhibited by compounds such as adenosine or NMN. The nadN gene product was characterized as an NAD-nucleotidase, responsible for the hydrolysis of NAD. H. influenzae hel and nadN mutants had defined growth deficiencies. For growth, the uptake and processing of the essential cofactors NADP and NAD required e(P4) and 5′-nucleotidase. In addition, adenosine was identified as a potent growth inhibitor of wild-type H. influenzae strains, when NADP was used as the sole source of nicotinamide-ribosyl.