| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Pathogenicity and Medical Microbiology |
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA1
Infectious Diseases Section, VA Connecticut Healthcare System, West Haven, CT, USA2
Author for correspondence: Brian Wong. Tel: +1 203 937 3446. Fax: +1 203 937 3476. e-mail: brian.wong{at}yale.edu
Cryptococcus neoformans, the causative agent of cryptococcosis, produces large amounts of mannitol in culture and in infected mammalian hosts. Although there is considerable indirect evidence that mannitol synthesis may be required for wild-type stress tolerance and virulence in C. neoformans, this hypothesis has not been tested directly. It has been proposed that mannitol-1-phosphate dehydrogenase (MPD) is required for fungal mannitol synthesis, but no MPD-deficient fungal mutants or cDNAs or genes encoding fungal MPDs have been described. Therefore, C. neoformans was purified from a 148 kDa homotetramer of 36 kDa subunits that catalysed the reaction mannitol1-phosphate+NAD
fructose 6-phosphate+NADH. Partial peptide sequences were used to isolate the corresponding cDNA and gene, and the deduced MPD protein was found to be homologous to the zinc-containing long-chain alcohol/polyol dehydrogenases. Lysates of Saccharomyces cerevisiae transformed with the cDNA of interest (but not vector-transformed controls) contained MPD catalytic activity. Lastly, Northern analyses demonstrated MPD mRNA in glucose- and mannitol-grown C. neoformans cells. Thus, MPD has been purified and characterized from C. neoformans, and the corresponding cDNA and gene (MPD1) cloned and sequenced. Availability of C. neoformans MPD1 should permit direct testing of the hypotheses that (i) MPD is required for mannitol biosynthesis and (ii) the ability to synthesize mannitol is essential for wild-type stress tolerance and virulence.
Keywords: mannitol-1-phosphate dehydrogenase, Cryptococcus neoformans, polyol/alcohol dehydrogenases
Abbreviations: M1Pase, mannitol-1-phosphatase; MPD, mannitol-1-phosphate dehydrogenase
The GenBank accession numbers for the nucleotide sequences for the C. neoformans mannitol-1-phosphate dehydrogenase cDNA and gene are AF175685 and AF186474, respectively.
This article has been cited by other articles:
|
|
 |
|
  J. M. Kingsbury and J. H. McCusker Threonine biosynthetic genes are essential in Cryptococcus neoformans Microbiology, September 1, 2008; 154(9): 2767 - 2775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Waterman, M. Hacham, J. Panepinto, G. Hu, S. Shin, and P. R. Williamson Cell Wall Targeting of Laccase of Cryptococcus neoformans during Infection of Mice Infect. Immun., February 1, 2007; 75(2): 714 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Garcia-Rivera, S. C. Tucker, M. Feldmesser, P. R. Williamson, and A. Casadevall Laccase Expression in Murine Pulmonary Cryptococcus neoformans Infection Infect. Immun., May 1, 2005; 73(5): 3124 - 3127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kingsbury, Z. Yang, T. M. Ganous, G. M. Cox, and J. H. McCusker Novel Chimeric Spermidine Synthase-Saccharopine Dehydrogenase Gene (SPE3-LYS9) in the Human Pathogen Cryptococcus neoformans Eukaryot. Cell, June 1, 2004; 3(3): 752 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Kingsbury, Z. Yang, T. M. Ganous, G. M. Cox, and J. H. McCusker Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 {degrees}C and in vivo Microbiology, May 1, 2004; 150(5): 1547 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Steen, S. Zuyderduyn, D. L. Toffaletti, M. Marra, S. J. M. Jones, J. R. Perfect, and J. Kronstad Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis Eukaryot. Cell, December 1, 2003; 2(6): 1336 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Iwamoto, H. Kawanobe, T. Ikawa, and Y. Shiraiwa Characterization of Salt-Regulated Mannitol-1-Phosphate Dehydrogenase in the Red Alga Caloglossa continua Plant Physiology, October 1, 2003; 133(2): 893 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. G. Ruijter, M. Bax, H. Patel, S. J. Flitter, P. J. I. van de Vondervoort, R. P. de Vries, P. A. vanKuyk, and J. Visser Mannitol Is Required for Stress Tolerance in Aspergillus niger Conidiospores Eukaryot. Cell, August 1, 2003; 2(4): 690 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Kavanagh, M. Klimacek, B. Nidetzky, and D. K. Wilson Crystal Structure of Pseudomonas fluorescens Mannitol 2-Dehydrogenase Binary and Ternary Complexes. SPECIFICITY AND CATALYTIC MECHANISM J. Biol. Chem., November 1, 2002; 277(45): 43433 - 43442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, R. C. Pascon, A. Alspaugh, G. M. Cox, and J. H. McCusker Molecular and genetic analysis of the Cryptococcus neoformans MET3 gene and a met3 mutant Microbiology, August 1, 2002; 148(8): 2617 - 2625. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
