Biomedical Engineering Reference
In-Depth Information
group of ceramide (Wells et al. 1996). These are under the control of various
genes including the
IPT
1 gene. A comparison of the
IPT
1 sequence from
S.
cerevisiae
and a partial sequence from
C. albicans
revealed identical motifs.
Depletion of the
IPT
1 gene (Δ
ipt
1 mutants
)
in
C. albicans
strain was shown
to increase the sensitivity of the yeast to several drugs and to reduce its
ability to form hyphae (Prasad et al. 2005).
The
IPT
1 gene also plays an important role in
C. albicans
interaction
with human cells. In a recent study using a gingival epithelial cell culture,
we reported that wild-type
Candida
strain adhered to the cells and was
distributed throughout the culture. However, a few Δ
ipt
1 mutant individual
Candida
cells were observed on the monolayer culture. Colony-forming
unit analyses showed a low
Candida
density (less than 20 x 10
4
) in a Δ
ipt
1
mutant-infected monolayer culture, compared to that obtained in a wild-
type (250 x 10
4
) infected culture. In addition, hyphal forms were present in
the cell cultures infected with the wild-type strain while none were observed
in the culture pulsed with the Δ
ipt
1 mutant strain (Rouabhia et al. 2010).
An engineered human oral mucosa model that mimicked normal human
gingival tissue confi rmed our results with monolayer cultures. As is shown
in
Figure 6,
the Δ
ipt
1 mutant strain was unable to adhere to the tissue to
form biofi lm. This non-adhesion and the strain's inability to change form
may therefore reduce the virulence of
C. albicans
. Data suggest that the
IPT1
gene modulates
C. albicans
interaction with host cells and tissue which may
promote its virulence.
CONCLUSIONS AND FUTURE DIRECTIONS
C. albicans
is a major fungal pathogen of humans (Peleg et al. 2010, van
de Veerdonk et al. 2010). Its pathogenicity/virulence is under the control
of numerous genes. Many studies using
in vitro
and
in vivo
experimental
models have investigated the activation of
C. albicans
genes. Some of
these genes are associated with signifi cant changes at the cellular level,
such as yeast/hypha morphogenesis and are clearly key players in the
infection process.
Of great interest is the specifi city of the genes. Some of them are
required in the early phase (adhesion), while others are involved in
growth, morphological changes and invasion; therefore, genes are required
throughout the entire infection process. Several genes are activated
simultaneously during the adhesion process, while some are activated
simultaneously during the invasion process. This suggests a functional gene
redundancy that must be investigated to acquire a better understanding of
C. albicans
physiology and pathogenesis. IPT1, PMT1 and PMT6 genes, for
example, are separately involved in the adhesive potential of
C. albicans,
but
which
one comes fi rst? What happens if they are all absent? Does
C. albicans
