Production of the hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis.
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.
Wong
B
B
Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio.
Perfect
J R
JR
Beggs
S
S
Wright
K A
KA
D000818:Animals; D000946:Antigens, Fungal / Q000134:cerebrospinal fluid; D003453:Cryptococcosis / Q000378:metabolism*; D003454:Cryptococcus / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000276:immunology / Q000378:metabolism*; D008353:Mannitol / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008581:Meningitis / Q000378:metabolism* / Q000382:microbiology; D011817:Rabbits
D000946:Antigens, Fungal; D008353:Mannitol