This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kemmer, G.
Right arrow Articles by Reidl, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kemmer, G.
Right arrow Articles by Reidl, J.

 Previous Article  |  Next Article 

Journal of Bacteriology, July 2001, p. 3974-3981, Vol. 183, No. 13
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.13.3974-3981.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

NadN and e (P4) Are Essential for Utilization of NAD and Nicotinamide Mononucleotide but Not Nicotinamide Riboside in Haemophilus influenzae

Gabriele Kemmer,1 Thomas J. Reilly,2 Joachim Schmidt-Brauns,1 Gary W. Zlotnik,3 Bruce A. Green,3 Michael J. Fiske,3 Mark Herbert,4 Anita Kraiß,1 Stefan Schlör,1 Arnold Smith,2 and Joachim Reidl1,*

Zentrum für Infektionsforschung, Universität Würzburg, 97070 Würzburg, Germany1; University of Missouri, Columbia, Missouri2; Wyeth-Lederle Vaccines, West Henrietta, New York 14586-97283; and Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom4

Received 22 January 2001/Accepted 12 April 2001

Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5'-nucleotidase activity. The e (P4) protein is also shown to have NMN 5'-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed.

* Corresponding author. Mailing address: Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany. Phone: (49) 931 312153. Fax: (49) 931 312578. E-mail: joachim.reidl{at}mail.uni-wuerzburg.de.

Journal of Bacteriology, July 2001, p. 3974-3981, Vol. 183, No. 13
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.13.3974-3981.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Gawronski, J. D., Wong, S. M. S., Giannoukos, G., Ward, D. V., Akerley, B. J. (2009). Tracking insertion mutants within libraries by deep sequencing and a genome-wide screen for Haemophilus genes required in the lung. Proc. Natl. Acad. Sci. USA 106: 16422-16427 [Abstract] [Full Text]  
  • Lu, S.-P., Kato, M., Lin, S.-J. (2009). Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae. J. Biol. Chem. 284: 17110-17119 [Abstract] [Full Text]  
  • Reilly, T. J., Chance, D. L., Calcutt, M. J., Tanner, J. J., Felts, R. L., Waller, S. C., Henzl, M. T., Mawhinney, T. P., Ganjam, I. K., Fales, W. H. (2009). Characterization of a Unique Class C Acid Phosphatase from Clostridium perfringens. Appl. Environ. Microbiol. 75: 3745-3754 [Abstract] [Full Text]  
  • Hoopman, T. C., Wang, W., Brautigam, C. A., Sedillo, J. L., Reilly, T. J., Hansen, E. J. (2008). Moraxella catarrhalis Synthesizes an Autotransporter That Is an Acid Phosphatase. J. Bacteriol. 190: 1459-1472 [Abstract] [Full Text]  
  • Vogl, C., Grill, S., Schilling, O., Stulke, J., Mack, M., Stolz, J. (2007). Characterization of Riboflavin (Vitamin B2) Transport Proteins from Bacillus subtilis and Corynebacterium glutamicum. J. Bacteriol. 189: 7367-7375 [Abstract] [Full Text]  
  • Gerlach, G., Reidl, J. (2006). NAD+ utilization in pasteurellaceae: simplification of a complex pathway.. J. Bacteriol. 188: 6719-6727 [Full Text]  
  • Merdanovic, M., Sauer, E., Reidl, J. (2005). Coupling of NAD+ Biosynthesis and Nicotinamide Ribosyl Transport: Characterization of NadR Ribonucleotide Kinase Mutants of Haemophilus influenzae. J. Bacteriol. 187: 4410-4420 [Abstract] [Full Text]  
  • Grose, J. H., Bergthorsson, U., Xu, Y., Sterneckert, J., Khodaverdian, B., Roth, J. R. (2005). Assimilation of Nicotinamide Mononucleotide Requires Periplasmic AphA Phosphatase in Salmonella enterica. J. Bacteriol. 187: 4521-4530 [Abstract] [Full Text]  
  • Grose, J. H., Bergthorsson, U., Roth, J. R. (2005). Regulation of NAD Synthesis by the Trifunctional NadR Protein of Salmonella enterica. J. Bacteriol. 187: 2774-2782 [Abstract] [Full Text]  
  • Sauer, E., Merdanovic, M., Price Mortimer, A., Bringmann, G., Reidl, J. (2004). PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine in Haemophilus influenzae. Antimicrob. Agents Chemother. 48: 4532-4541 [Abstract] [Full Text]  
  • Herbert, M., Sauer, E., Smethurst, G., Kraiss, A., Hilpert, A.-K., Reidl, J. (2003). Nicotinamide Ribosyl Uptake Mutants in Haemophilus influenzae. Infect. Immun. 71: 5398-5401 [Abstract] [Full Text]  
  • Andersen, C., Maier, E., Kemmer, G., Blass, J., Hilpert, A.-K., Benz, R., Reidl, J. (2003). Porin OmpP2 of Haemophilus influenzae Shows Specificity for Nicotinamide-derived Nucleotide Substrates. J. Biol. Chem. 278: 24269-24276 [Abstract] [Full Text]  
  • Kurnasov, O. V., Polanuyer, B. M., Ananta, S., Sloutsky, R., Tam, A., Gerdes, S. Y., Osterman, A. L. (2002). Ribosylnicotinamide Kinase Domain of NadR Protein: Identification and Implications in NAD Biosynthesis. J. Bacteriol. 184: 6906-6917 [Abstract] [Full Text]  
  • Singh, S. K., Kurnasov, O. V., Chen, B., Robinson, H., Grishin, N. V., Osterman, A. L., Zhang, H. (2002). Crystal Structure of Haemophilus influenzae NadR Protein. A BIFUNCTIONAL ENZYME ENDOWED WITH NMN ADENYLYLTRANSFERASE AND RIBOSYLNICOTINAMIDE KINASE ACTIVITIES. J. Biol. Chem. 277: 33291-33299 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»