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J. Biol. Chem., Vol. 278, Issue 3, 1713-1720, January 17, 2003
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From the Deletion of the kexin gene (KEX2) in
Candida albicans has a pleiotropic effect on phenotype and
virulence due partly to a defect in the expression of two major
virulence factors: the secretion of active aspartyl proteinases and the
formation of hyphae. kex2/kex2 mutants are
highly attenuated in a mouse systemic infection model and persist
within cultured macrophages for at least 24 h without causing
damage. Pathology is modest, with little disruption of kidney matrix.
The infecting mutant cells are largely confined to glomeruli, and are
aberrant in morphology. The complex phenotype of the deletion mutants
reflects a role for kexin in a wide range of cellular processes. Taking
advantage of the specificity of Kex2p cleavage, an algorithm we
developed to scan the 9168 open reading frames in Assembly 6 of the
C. albicans genome identified 147 potential substrates of
Kex2p. These include all previously identified substrates, including
eight secreted aspartyl proteinases, the exoglucanase Xog1p, the
immunodominant antigen Mp65, and the adhesin Hwp1p. Other putative
Kex2p substrates identified include several adhesins, cell wall
proteins, and hydrolases previously not implicated in
pathogenesis. Kexins also process fungal mating pheromones; a
modification of the algorithm identified a putative mating pheromone
with structural similarities to Saccharomyces cerevisiae
Inactivation of Kex2p Diminishes the Virulence of
Candida albicans*
§,
§¶,
,
,
**,
,
, and

Department of Stomatology, University of
California at San Francisco, California 94143-0422 and
Merck
Research Laboratories, Rahway, New Jersey 07065-0900
-factor.
*
This study was supported by National Institutes of Health
Grants A133317, RO1DE12940, P01 DE07946-15S2, and PO1 DE07946.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of
Stomatology, University of California, 521 Parnassus Avenue, Box 0422, San Francisco, CA 94243-0422. Tel.: 415-476-6845; Fax: 415-476-0664; Email: agabian@itsa.ucsf.edu.
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