Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata.
The pathogenic yeast Candida glabrata is able to bind in vitro to human epithelial cells. This interaction depends on expression of the adhesin Epa1p. The genome contains a number of EPA1 paralogues which localize to the subtelomeric regions of the C. glabrata. We have identified three hyperadherent mutants of C. glabrata. The first has an insertion adjacent to EPA7, an EPA1-related adhesin. The others disrupt the SIR3 and RIF1 genes of C. glabrata. We show that SIR3 and RIF1 are required for subtelomeric silencing in C. glabrata and that RIF1 regulates telomere length in C. glabrata. We show that the hyperadherent phenotype of the sir3Delta and rif1Delta deletion strains depends primarily on derepression of two novel members of the EPA gene family -EPA6 and EPA7. The sir3Delta and rif1Delta mutants show increased colonization of the kidney in a murine model of disseminated infection and this hypercolonization depends, at least in part, on derepression of EPA6 and EPA7. The analysis here is the first evidence that multiple EPA genes encode adhesins and demonstrates that transcription of at least two of these adhesins is regulated by subtelomeric silencing.
Castaño
Irene
I
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Pan
Shih-Jung
SJ
Zupancic
Margaret
M
Hennequin
Christophe
C
Dujon
Bernard
B
Cormack
Brendan P
BP
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D041221:Candida glabrata / Q000235:genetics*; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007668:Kidney; D037102:Lectins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure*; D014162:Transfection
D017931:DNA Primers; D005656:Fungal Proteins; D037102:Lectins; C120505:epithelial adhesin 1, Candida glabrata