COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans
Two-component histidine kinases recently have been found in eukaryotic organisms including fungi, slime molds, and plants. We describe the identification of a gene, COS1, from the opportunistic pathogen Candida albicans by using a PCR-based screening strategy. The sequence of COS1 indicates that it encodes a homolog of the histidine kinase Nik-1 from the filamentous fungus Neurospora crassa. COS1 is also identical to a gene called CaNIK1 identified in C. albicans by low stringency hybridization using CaSLN1 as a probe [Nagahashi, S., Mio, T., Yamada-Okabe, T., Arisawa, M., Bussey, H. & Yamada-Okabe, H. (1998) Microbiol. 44, 425-432]. We assess the function of COS1/CaNIK1 by constructing a diploid deletion mutant. Mutants lacking both copies of COS1 appear normal when grown as yeast cells; however, they exhibit defective hyphal formation when placed on solid agar media, either in response to nutrient deprivation or serum. In constrast to the Delta nik-1 mutant, the Delta cos1/Delta cos1 mutant does not demonstrate deleterious effects when grown in media of high osmolarity; however both Delta nik-1 and Delta cos1/Delta cos1 mutants show defective hyphal formation. Thus, as predicted for Nik-1, Cos1p may be involved in some aspect of hyphal morphogenesis and may play a role in virulence properties of the organism.
Additional Information© 1998 by the National Academy of Sciences Contributed by Melvin I. Simon, April 3, 1998 Data deposition: The genomic DNA sequence encoding COS1 reported in this paper has been deposited in the GenBank database (accession no. U69886) We thank Brendan Cormack (Stanford University) for the gift of strains and plasmids as well as technical advice. We also thank Doreen Harcus (CNRC-NRC, Canada) for the gift of plamids and strains, Jacqueline Agnan for technical assistance in cloning COS1, and members of the Cal Tech Sequencing facility for their assistance in DNA sequencing. This work was funded by National Institutes of Health Grants AI 19296 (M.I.S.) and AI 33354 (C.P.S.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Published - ALEpnas98.pdf