Biomedical Engineering Reference
In-Depth Information
Pmt
6 gene
Mutations of
Pmt
6
genes did not promote
C. albicans
death, but rather
inhibited its morphological changes in the yeast-to-hyphae transition
(Timpel et al. 1998; Timpel et al. 2000). Heterozygous
Pmt
6/
pmt
6 strains,
as well as homozygous
pmt
6/
pmt
6 mutants were shown to display normal
hyphal formation under certain culture conditions (Timpel et al. 1998). Of
interest is that Pmt6 phenotype can be corrected by an over-expression
of Cek1p, Cph1p, Tpk2p and Efg1p signaling molecules (Timpel et
al. 2000). This suggests the involvement of an upstream mediator or
mediators that must be determined. Reintroducing
Pmt
6 into the
Pmt
6/
Pmt
6 mutant restored
morphogenesis as expected; in addition,
Pmt
1
expression complemented the
Pmt
6 mutant phenotype, which suggests
common functions of Pmt6p and Pmt1p. Pmt6p may have narrower
substrate specifi city than does Pmt1p, as
Pmt
6 over-expression did not
complement the
Pmt
1 phenotype (Timpel et al. 2000). With one or two
Pmt
6 mutant alleles,
C. albicans
was shown to grow well in the presence
of a low concentration of hygromycin B but was inhibited in the presence
of a higher concentration of 200 µg/ml (Timpel et al. 2000). This effect
is limited to hygromycin B, as
Pmt
6 mutant was not highly sensitive to
other antifungal drugs including nystatin, amphotericin
B, clotrimazole,
etc. (Timpel et al. 1998).
In our engineered human oral mucosa, we demonstrated that
Pmt
6
mutants were virulent, resulting in signifi cant tissue damage similar to
that of wild-type strains, whereas with engineered epidermal tissue,
Pmt
6
was shown to be less virulent than were the wild-type strains (Rouabhia
et al. 2005). This suggests that
Pmt
6 has an environment-specifi c role that
remains to be elucidated.
ROLE OF THE
IPT
1 GENE AND PROTEIN IN
C. ALBICANS
PATHOGENESIS
Sphingolipids, important components of the eukaryotic membrane,
are key players in cell physiology through their role as signal transduction
intermediates in the regulatory pathways occurring in yeast (
Candida
and
S. cerevisae
). Several studies have reported that sphingolipids are under
the control of various genes, including inositolphosphotransferase 1 (
IPT
1
)
(Im et al. 2003, Hechtberger et al. 1994)
.
In
S. cerevisiae
yeast,
IPT
1 has a
small—if only slight—effect on cell growth but an active role on yeast
phenotype and sensitivity to antifungal agents. Indeed,
IPT
1 deletion leads
to a complete loss of M(IP)2Cs and affects sensitivity to drugs, such as
Dahlia merckii
antimicrobial peptide 1 (DmAMP1) (Thevissen et al. 2000)
and syringomycin E (Im et al. 2003). M(IP)2Cs are found primarily in
