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Infection and Immunity, June 2000, p. 3485-3490, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of Hyphal Formation in Interactions of Candida albicans with Endothelial Cells

Quynh T. Phan,1 Paul H. Belanger,1 and Scott G. Filler1,2,*

St. John's Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502,1 and University of California at Los Angeles School of Medicine, Los Angeles, California 900242

Received 20 December 1999/Returned for modification 12 February 2000/Accepted 17 March 2000

The ability to change from yeast to hyphal morphology is a major virulence determinant of Candida albicans. Mutants with defined defects in filamentation regulatory pathways have reduced virulence in mice. However, is it poorly understood why hyphal formation is critical for C. albicans to cause hematogenously disseminated infections. We used recently constructed mutants to examine the role of hyphal formation in the interactions of C. albicans with endothelial cells in vitro. These interactions included the ability of the mutants to invade and injure endothelial cells. Because the formation of hyphae may influence the host inflammatory response to C. albicans, we also investigated the capacity of these mutants to stimulate endothelial cells to express E-selectin and intercellular adhesion molecule 1. We infected endothelial cells with C. albicans strains containing homozygous null mutations in the following filamentation regulatory genes: CLA4, CPH1, EFG1, and TUP1. Whereas the wild-type strain formed true hyphae on endothelial cells, we found that neither the Delta efg1 nor the Delta cph1 Delta efg1 double mutant germinated. The Delta tup1 mutant formed only pseudohyphae. We also found that the Delta efg1, Delta cph1 Delta efg1, and Delta tup1 mutants had significantly reduced capacities to invade and injure endothelial cells. Therefore, Efg1p and Tup1p contribute to virulence by regulating hyphal formation and the factors that enable C. albicans to invade and injure endothelial cells. With the exception of the Delta cph1 Delta efg1 mutant, all other mutants stimulated endothelial cells to express at least one of the leukocyte adhesion molecules. Therefore, the combined activities of Cph1p and Efg1p are required for C. albicans to stimulate a proinflammatory response in endothelial cells.

* Corresponding author. Mailing address: Division of Infectious Diseases, Harbor-UCLA Research and Education Institute, Bldg. RB-2, 1124 West Carson St., Torrance, CA 90502. Phone: (310) 222-6426. Fax: (310) 782-2016. E-mail: sfiller{at}ucla.edu.

Infection and Immunity, June 2000, p. 3485-3490, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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