Deletion of the CaBIG1 gene reduces beta-1,6-glucan synthesis, filamentation, adhesion, and virulence in Candida albicans.
The human fungal pathogen Candida albicans is able to change its shape in response to various environmental signals. We analyzed the C. albicans BIG1 homolog, which might be involved in beta-1,6-glucan biosynthesis in Saccharomyces cerevisiae. C. albicans BIG1 is a functional homolog of an S. cerevisiae BIG1 gene, because the slow growth of an S. cerevisiae big1 mutant was restored by introduction of C. albicans BIG1. CaBig1p was expressed constitutively in both the yeast and hyphal forms. A specific localization of CaBig1p at the endoplasmic reticulum or plasma membrane similar to the subcellular localization of S. cerevisiae Big1p was observed in yeast form. The content of beta-1,6-glucan in the cell wall was decreased in the Cabig1Delta strain in comparison with the wild-type or reconstituted strain. The C. albicans BIG1 disruptant showed reduced filamentation on a solid agar medium and in a liquid medium. The Cabig1Delta mutant showed markedly attenuated virulence in a mouse model of systemic candidiasis. Adherence to human epithelial HeLa cells and fungal burden in kidneys of infected mice were reduced in the Cabig1Delta mutant. Deletion of CaBIG1 abolished hyphal growth and invasiveness in the kidneys of infected mice. Our results indicate that adhesion failure and morphological abnormality contribute to the attenuated virulence of the Cabig1Delta mutant.
Umeyama
Takashi
T
Laboratory of Mycology, Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Kaneko
Aki
A
Watanabe
Hiroshi
H
Hirai
Asuka
A
Uehara
Yoshimasa
Y
Niimi
Masakazu
M
Azuma
Masayuki
M
D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002473:Cell Wall / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D017353:Gene Deletion; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D025301:Hyphae / Q000235:genetics / Q000254:growth & development*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D047071:beta-Glucans / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
C510015:BIG1 protein, Candida albicans; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D047071:beta-Glucans; C064197:beta-1,6-glucan