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Journal of Bacteriology, July 2005, p. 4410-4420, Vol. 187, No. 13
0021-9193/05/$08.00+0     doi:10.1128/JB.187.13.4410-4420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Coupling of NAD⁺ Biosynthesis and Nicotinamide Ribosyl Transport: Characterization of NadR Ribonucleotide Kinase Mutants of Haemophilus influenzae

Institut für Hygiene und Mikrobiologie, Universität Würzburg, Josef Schneider Str. 2, E1, 97080 Würzburg, Germany

Received 3 February 2005/ Accepted 21 March 2005

Previously, we characterized a pathway necessary for the processing of NAD⁺ and for uptake of nicotinamide riboside (NR) in Haemophilus influenzae. Here we report on the role of NadR, which is essential for NAD⁺ utilization in this organism. Different NadR variants with a deleted ribonucleotide kinase domain or with a single amino acid change were characterized in vitro and in vivo with respect to cell viability, ribonucleotide kinase activity, and NR transport. The ribonucleotide kinase mutants were viable only in a nadV⁺ (nicotinamide phosphoribosyltransferase) background, indicating that the ribonucleotide kinase domain is essential for cell viability in H. influenzae. Mutations located in the Walker A and B motifs and the LID region resulted in deficiencies in both NR phosphorylation and NR uptake. The ribonucleotide kinase function of NadR was found to be feedback controlled by NAD⁺ under in vitro conditions and by NAD⁺ utilization in vivo. Taken together, our data demonstrate that the NR phosphorylation step is essential for both NR uptake across the inner membrane and NAD⁺ synthesis and is also involved in controlling the NAD⁺ biosynthesis rate.

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