Biomedical Engineering Reference
In-Depth Information
its pathogenic potential, as previously suggested (Budtz-Jorgensen 1978,
Sakki et al. 1997).
Candida
Gene Activation
The identification of
Candida
as the etiologic agent for candidiasis,
particularly in immunocompromised hosts, has resulted in a wide range
of initiatives to assess its virulent properties in relation to multiple gene
activation. Multiple
Candida
genes are regulated under environmental
culture conditions such as plastic, temperature, pH and culture medium.
Candida
morphological changes involve some specifi c genes (Richardson
1991). It is also important to note that over 500 genes are regulated during
the interaction between
Candida
and the host, subsequent to the infection
process. Some genes are involved in
Candida
adhesion (Sundstrom 1999)
or
Candida
morphological changes (San-Blas et al., 2000), while others are
involved in
Candida
biofi lm formation (Nobile and Mitchell 2006) and all
of them are involved in
Candida
pathogenesis. In this review, we address
the role of three genes in the pathogenesis of
C. albicans
.
ROLE OF THE
ADH1
GENE AND PROTEIN IN
C. ALBICANS
PATHOGENESIS
ADH
genes and proteins from yeasts, including
Candida,
were previously
sequenced and characterized
(Bertram et al. 1996). Three
ADH
genes
encoding one cytoplasmic and two mitochondrial enzymes were cloned
from
Candida boidinii
(Park et al. 2006). A purifi ed methyl formate synthase
from
C. boidinii
belonged to the NAD+-dependent class III alcohol
dehydrogenase family (Murdanoto et al. 1997). The
C. albicans ADH
1
gene
encoded a 350 amino acid enzyme with high homologies to yeast
ADH
s
(Bertram et al. 1996).
C. albicans ADH
2
gene was identifi ed by genome
sequencing (Jones et al. 2004).
In
C. albicans
as individual cells, Adh1p was shown to have multiple
roles, including interactions with the host immune system (Pitarch et al.
2004) and binding host proteins (Klotz et al. 2001). Adh1p is the
C. albicans
cell wall protein able to bind plasminogen, which leads to the release of
activated
plasmin (Crowe et al. 2003). Because plasmin is known to display
proteolytic
activity, this suggests that Adh1p may promote the fungal
invasion of host tissues. Further investigations are mandatory to shed light
on coagulation/wound repair in relation to
Candida
infection.
The
ADH
gene also plays a signifi cant role in
Candida
infection/
virulence by inhibiting biofi lm formation. Indeed,
ADH1
was shown to
downregulate biofi lm formation by
C. albicans
(Mukherjee et al. 2006),