Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1990 Jun;58(6):1664–1670. doi: 10.1128/iai.58.6.1664-1670.1990

Production of the hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis.

B Wong 1, J R Perfect 1, S Beggs 1, K A Wright 1
PMCID: PMC258702  PMID: 2111284

Abstract

We studied the ability of Cryptococcus neoformans to produce the hexitol D-mannitol in vitro and in rabbits with experimental meningitis. Twelve of twelve human isolates of C. neoformans produced D-mannitol in yeast nitrogen base plus 1% glucose and released D-mannitol into the medium. In a pilot study, pooled cerebrospinal fluid (CSF) from cortisone-treated rabbits given 3 x 10(7) C. neoformans H99 intracisternally contained more D-mannitol (identified by gas chromatography and enzymatically) than CSF from normal controls or cortisone-untreated rabbits with self-limited meningitis. In a second experiment, cortisone-treated rabbits given C. neoformans intracisternally had significantly higher CSF D-mannitol concentrations than controls given cortisone alone at 4, 6, and 8 days after infection. Moreover, log10 CSF D-mannitol correlated well with log10 CSF CFU (r = 0.81) and log10 CSF cryptococcal antigen titers (r = 0.78). Lastly, the initial volume of distribution and elimination half-life of D-mannitol given intracisternally to normal rabbits suggested that D-mannitol was distributed in total CSF and was removed by CSF bulk flow. Thus, C. neoformans produces D-mannitol in vitro and in vivo, and D-mannitol is a quantitative marker for experimental cryptococcal meningitis. D-Mannitol produced by C. neoformans may also contribute to brain edema and interfere with phagocyte killing by scavenging hydroxyl radicals.

Full text

PDF
1664

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett J. E., Dismukes W. E., Duma R. J., Medoff G., Sande M. A., Gallis H., Leonard J., Fields B. T., Bradshaw M., Haywood H. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis. N Engl J Med. 1979 Jul 19;301(3):126–131. doi: 10.1056/NEJM197907193010303. [DOI] [PubMed] [Google Scholar]
  2. Bernard E. M., Wong B., Armstrong D. Stereoisomeric configuration of arabinitol in serum, urine, and tissues in invasive candidiasis. J Infect Dis. 1985 Apr;151(4):711–715. doi: 10.1093/infdis/151.4.711. [DOI] [PubMed] [Google Scholar]
  3. Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
  4. Diamond R. D., Root R. K., Bennett J. E. Factors influencing killing of Cryptococcus neoformans by human leukocytes in vitro. J Infect Dis. 1972 Apr;125(4):367–376. doi: 10.1093/infdis/125.4.367. [DOI] [PubMed] [Google Scholar]
  5. Gold J. W., Wong B., Bernard E. M., Kiehn T. E., Armstrong D. Serum arabinitol concentrations and arabinitol/creatinine ratios in invasive candidiasis. J Infect Dis. 1983 Mar;147(3):504–513. doi: 10.1093/infdis/147.3.504. [DOI] [PubMed] [Google Scholar]
  6. Kiehn T. E., Bernard E. M., Gold J. W., Armstrong D. Candidiasis: detection by gas-liquid chromatography of D-arabinitol, a fungal metabolite, in human serum. Science. 1979 Nov 2;206(4418):577–580. doi: 10.1126/science.493963. [DOI] [PubMed] [Google Scholar]
  7. Kovacs J. A., Kovacs A. A., Polis M., Wright W. C., Gill V. J., Tuazon C. U., Gelmann E. P., Lane H. C., Longfield R., Overturf G. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Oct;103(4):533–538. doi: 10.7326/0003-4819-103-4-533. [DOI] [PubMed] [Google Scholar]
  8. Neuberger M. S., Patterson R. A., Hartley B. S. Purification and properties of Klebsiella aerogenes D-arabitol dehydrogenase. Biochem J. 1979 Oct 1;183(1):31–42. doi: 10.1042/bj1830031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Onishi H., Suzuki T. Production of D-mannitol and glycerol by yeasts. Appl Microbiol. 1968 Dec;16(12):1847–1852. doi: 10.1128/am.16.12.1847-1852.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Perfect J. R., Lang S. D., Durack D. T. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol. 1980 Oct;101(1):177–194. [PMC free article] [PubMed] [Google Scholar]
  11. Pitkänen E., Bardy A., Pasternack A., Servo C. Plasma, red cell and cerebrospinal fluid concentrations of mannitol and sorbital in patients with severe chronic renal failure. Ann Clin Res. 1976 Dec;8(6):368–373. [PubMed] [Google Scholar]
  12. Prockop L. D., Fishman R. A. Experimental pneumococcal meningitis. Permeability changes influencing the concentration of sugars and macromolecules in cerebrospinal fluid. Arch Neurol. 1968 Nov;19(5):449–463. doi: 10.1001/archneur.1968.00480050019001. [DOI] [PubMed] [Google Scholar]
  13. Roboz J., Suzuki R., Holland J. F. Quantification of arabinitol in serum by selected ion monitoring as a diagnostic technique in invasive candidiasis. J Clin Microbiol. 1980 Oct;12(4):594–601. doi: 10.1128/jcm.12.4.594-601.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rosen H., Klebanoff S. J. Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. J Exp Med. 1979 Jan 1;149(1):27–39. doi: 10.1084/jem.149.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Servo C., Palo J., Pitkänen E. Polyols in the cerebrospinal fluid and plasma of neurological, diabetic and uraemic patients. Acta Neurol Scand. 1977 Aug;56(2):111–116. doi: 10.1111/j.1600-0404.1977.tb01416.x. [DOI] [PubMed] [Google Scholar]
  16. TOUSTER O., SHAW D. R. Biochemistry of the acyclic polyols. Physiol Rev. 1962 Apr;42:181–225. doi: 10.1152/physrev.1962.42.2.181. [DOI] [PubMed] [Google Scholar]
  17. Wong B., Bernard E. M., Gold J. W., Fong D., Silber A., Armstrong D. Increased arabinitol levels in experimental candidiasis in rats: arabinitol appearance rates, arabinitol/creatinine ratios, and severity of infection. J Infect Dis. 1982 Sep;146(3):346–352. doi: 10.1093/infdis/146.3.346. [DOI] [PubMed] [Google Scholar]
  18. Wong B., Brauer K. L. Enantioselective measurement of fungal D-arabinitol in the sera of normal adults and patients with candidiasis. J Clin Microbiol. 1988 Sep;26(9):1670–1674. doi: 10.1128/jcm.26.9.1670-1674.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wong B., Brauer K. L., Tsai R. R., Jayasimhulu K. Increased amounts of the Aspergillus metabolite D-mannitol in tissue and serum of rats with experimental aspergillosis. J Infect Dis. 1989 Jul;160(1):95–103. doi: 10.1093/infdis/160.1.95. [DOI] [PubMed] [Google Scholar]
  20. Wong B., Castellanos M. Enantioselective measurement of the Candida metabolite D-arabinitol in human serum using multi-dimensional gas chromatography and a new chiral phase. J Chromatogr. 1989 Oct 27;495:21–30. doi: 10.1016/s0378-4347(00)82606-7. [DOI] [PubMed] [Google Scholar]
  21. Zuger A., Louie E., Holzman R. S., Simberkoff M. S., Rahal J. J. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment. Ann Intern Med. 1986 Feb;104(2):234–240. doi: 10.7326/0003-4819-104-2-234. [DOI] [PubMed] [Google Scholar]
  22. Zuger A., Schuster M., Simberkoff M. S., Rahal J. J., Holzman R. S. Maintenance amphotericin B for cryptococcal meningitis in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988 Oct 1;109(7):592–593. doi: 10.7326/0003-4819-109-7-592. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES