Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Poster number: 18
A C-terminal hyphal activation motif of the transcription
factor Tec1p is essential for biofilm formation and
nematode infection in Candida albicans
Schröppel K., Singh A., Dietsche T., Eickhoff H., Wiesmüller K.-H., Fischer
K., and Abu Rayyan W.
Institute of Medical Microbiology and Hygiene, University Hospital and Clinics, University of
Tübingen, Tübingen, Germany
Hyphal formation of Candida albicans is a prerequisite for penetration of host
tissues. The formation of biofilms allows this pathogen to persist and to increase
resistance against anti-fungal compounds. In order to define a structure function
relationship for the important transcription factor Tec1p, we integrated modified
open reading frames (ORFs) of the wild type TEC1 under the control of the C.
albicans adapted reverse Tet-dependent transactivator (rtTA) into the tec1/tec1
mutant. We screened a library of such C. albicans mutants for their ability of in vitro
biofilm formation and morphogenetic development, and examined their virulence
in a nematode host using C. elegans as an infection model. Additionally, we
characterized the antifungal activity of EMC120B12, a novel (S)-2-aminoalkyl
benzimidazole derivative, against the library of C. albicans TEC1 mutants in vitro
and in vivo. In comparison to a full length TEC1 ORF, the ORF constructs either with
a deletion of the C-terminus from position 637 aa to the stop codon at 744 aa or a
deletion of the TEA domain from 216 to 244 aa showed abrogation in restoring
hyphal growth and biofilm formation in the tec1/tec1 mutant. Interestingly, the
tec1/tec1 phenotype was rescued in a mutant containing an ORF with an additional
72 aa that spanned the region from 1 to 709 aa. The deletion of the proposed Cterminal
hyphal activation motif CHAM of Tec1p did not affect DNA binding to a
TEA consensus sequence TCS probe.
In the C. elegans infection model we found that the C. albicans mutant lacking
CHAM showed less virulence in terms of hyphal invasion and killing of the nematode
host. During in vivo infection studies, we could demonstrate that EMC120B12 can
inhibit filamentation of C. albicans and prolong survival of the C. albicans infected
nematodes.
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