Urease as a Virulence Factor in Experimental Cryptococcosis

DOI Web Site 被引用文献4件
  • Gary M. Cox
    <!--label omitted: 1-->Division of Infectious Disease, Department of Medicine, Duke University Medical Center, Durham, North Carolina 277101;
  • Jean Mukherjee
    <!--label omitted: 2-->Division of Infectious Diseases, Department of Medicine, and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 104612; and
  • Garry T. Cole
    <!--label omitted: 3-->Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 436143
  • Arturo Casadevall
    <!--label omitted: 2-->Division of Infectious Diseases, Department of Medicine, and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 104612; and
  • John R. Perfect
    <!--label omitted: 1-->Division of Infectious Disease, Department of Medicine, Duke University Medical Center, Durham, North Carolina 277101;
  • T. R. Kozel
    editor

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<jats:title>ABSTRACT</jats:title> <jats:p> Urease catalyzes the hydrolysis of urea to ammonia and carbamate and has been found to be an important pathogenic factor for certain bacteria. <jats:italic>Cryptococcus neoformans</jats:italic> is a significant human pathogenic fungus that produces large amounts of urease; thus we wanted to investigate the importance of urease in the pathogenesis of cryptococcosis. We cloned and sequenced the genomic locus containing the single-copy <jats:italic>C. neoformans</jats:italic> urease gene ( <jats:italic>URE1</jats:italic> ) and used this to disrupt the native <jats:italic>URE1</jats:italic> in the serotype A strain H99. The <jats:italic>ure1</jats:italic> mutant strains were found to have in vitro growth characteristics, phenoloxidase activity, and capsule size similar to those of the wild type. Comparison of a <jats:italic>ure1</jats:italic> mutant with H99 after intracisternal inoculation into corticosteroid-treated rabbits revealed no significant differences in colony counts recovered from the cerebrospinal fluid. However, when these two strains were compared in both the murine intravenous and inhalational infection models, there were significant differences in survival. Mice infected with a <jats:italic>ure1</jats:italic> strain lived longer than mice infected with H99 in both models. The <jats:italic>ure1</jats:italic> strain was restored to urease positivity by complementation with <jats:italic>URE1</jats:italic> , and two resulting transformants were significantly more pathogenic than the <jats:italic>ure1</jats:italic> strain. Our results suggest that urease activity is involved in the pathogenesis of cryptococcosis but that the importance may be species and/or infection site specific. </jats:p>

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