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Infection and Immunity, November 1999, p. 6034-6039, Vol. 67, No. 11
Division of Infectious Diseases, University
of Illinois at Chicago, Chicago, Illinois
60612,1 and Department of
Microbiology and Immunology, Southern Illinois University,
Springfield, Illinois 627022
Received 3 May 1999/Returned for modification 19 June 1999/Accepted 10 August 1999
While laccase of Cryptococcus neoformans is implicated
in the virulence of the organism, our recent studies showing absence of
melanin in the infected mouse brain has led us to a search for
alternative roles for laccase in cryptococcosis. We investigated the
role of laccase in protection of C. neoformans against
murine alveolar macrophage (AM)-mediated antifungal activity by using a
pair of congenic laccase-positive (2E-TUC) and laccase-deficient (2E-TU) strains. The laccase-positive cells with laccase derepression were more resistant to the antifungal activity of AM than a
laccase-deficient strain ([28.9 ± 1.2]% versus [40.2 ± 2.6]% killing). Addition of L-dopa to
Cryptococcus to produce melanin in a laccase-positive strain resulted in a slight increase in protection of C. neoformans from the antifungal activity of macrophages
([25.4 ± 3.4]% versus [28.9 ± 1.2]% killing).
Recombinant cryptococcal laccase exhibited iron oxidase activity in
converting Fe(II) to Fe(III). Moreover, recombinant laccase inhibited
killing of C. neoformans by hydroxyl radicals catalyzed by
iron in a cell-free system. Addition of the hydroxyl radical scavenger
mannitol or dimethyl sulfoxide to AMs prior to the introduction of
cryptococcal cells decreased killing of both strains and reduced the
difference in susceptibility between the laccase-positive and
laccase-deficient strains. Furthermore, laccase-mediated protection
from AM killing was inhibited by the addition of Fe(II), presumably by
overcoming the effects of the iron oxidase activity of cryptococcal
laccase. These results suggest that the iron oxidase activity of
laccase may protect C. neoformans from macrophages by
oxidation of phagosomal iron to Fe(III) with a resultant decrease in
hydroxyl radical formation.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Laccase Protects Cryptococcus neoformans
from Antifungal Activity of Alveolar Macrophages
*
Corresponding author. Mailing address: Rm. 888, Bldg.
910, m/c 735, 808 S. Wood St., University of Illinois at Chicago,
Chicago, IL 60612. Phone: (312) 996-6070. Fax: (312) 413-1657. E-mail: prw{at}uic.edu.
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