Ja. Calera et R. Calderone, Histidine kinase, two-component signal transduction proteins of Candida albicans and the pathogenesis of candidosis, MYCOSES, 42, 1999, pp. 49-53
Candida albicans is an important pathogen of the immunocompromised patient.
Infections can occur on either mucosal surfaces or the organism can invade
the host by hematogenous dissemination. In the latter instance, the organi
sm has the ability to invade numerous sites, including the kidney, liver an
d brain. Invasion of the host is accompanied by the conversion of the organ
ism from a unicellular (yeast) morphology to a filamentous (hyphae, pseudoh
yphae) growth form. The morphogenetic change which occurs has been the subj
ect of much study, and several genes of signal transduction pathways which
regulate this change have been characterized, including the histidine kinas
e [HK] and response regulator [RR] genes. The HKs of C. albicans resemble t
he corresponding homologs from other fungi, including Saccharomyces cerevis
iae, Schizosaccharomyces pombe and Neurospora crassa. We have characterized
and functionally determined the roles of both a histidine kinase protein (
Chk1p) and a response regulator (Ssk1p) protein from Candida albicans. Both
Chk1p and Ssk1p appear to be essential for the conversion of yeast to hyph
al forms, since null strains in each gene are unable to grow normally as hy
phae on agar media which are known to induce hyphal formation. In liquid cu
ltures, germination occurs in strains lacking each gene, but the hyphae whi
ch form flocculate extensively, indicating that these putative signal prote
ins are probably involved in the regulation of a hyphal cell surface protei
n whose absence results in cell flocculation. Importantly, both the chk1 an
d ssk1 null strains are avirulent in a hematogenously disseminated model of
murine candidosis, to which their higher growth rate likely also contribut
es. Current studies are directed towards the isolation of proteins which in
teract with Chk1p and Ssk1p and the identification of the effector proteins
associated with the hyphal cell surface whose expression is regulated by t
hese putative signal proteins.