Involvement of ADH1, IPT1 and PMT Genes in Candida albicans Pathogenesis - Biotechnology of Fungal Genes - page 79

whereas the same gene upregulated the formation of biofi lm by S. aureus
(Becker et al. 2001). This versatility by ADH1 in different microbial biofi lms
may thus have an impact on the interactions between C. albicans and bacteria
in a mixed-species environment.
Hypothetically speaking, it is likely that by over-expressing ADH 1,
bacteria will enhance their ability to form biofilm while at the same
time inhibiting Candida biofi lm formation. Such a hypothesis requires
confi rmation to fully understand the specifi city of ADH expression in yeast
and bacteria.
The role of the ADH 1 gene on C. albicans biofi lm formation is confi rmed
by the Adh1 protein. Indeed, using molecular and biochemical approaches,
we showed that Adh1p restricted the ability of Candida to form biofi lm, as
revealed by enhanced biofi lm formation in response to the disruption of
the ADH 1 gene or the biochemical inhibition of the enzyme (Mukherjee
et al. 2006).
Compared to the parent strain, ADH 1 mutant Candida strain displays
reduced fi tness; this reduction may play an active role in the interaction of
C. albicans with bacteria existing in the environment and leading to mixed
biofi lm formation. In this regard, Hogan and Kolter (2002) suggested a link
between biofi lm formation and the activities of some eukaryotic-specifi c
virulence factors toward fungal cells and that the antagonism between
bacteria and fungi may contribute to the evolution and maintenance of
many pathogenesis-related genes.
In an extended investigation, the role of the ADH 1 gene in Candida 's
interaction with the host was confi rmed using engineered human oral
mucosa ( Fig. 4, Mukherjee et al. 2006). This investigation was the fi rst to
demonstrate a correlation between the activity of the ADH1 protein and
biofi lm formation on normal human tissue, such as oral mucosa, which
brings us closer to the clinical setting. The observation that an ADH 1 mutant
of C. albicans formed increased biofi lm (which may in turn promote tissue
invasion) suggests that biofi lm plays a role in the ability of Candida to
invade host tissues. It is likely that having the ability to form biofi lm in the
oral cavity enables Candida to transmigrate across the oral submucosa and
subsequently possibly cause systemic infection. As our study demonstrated
that the ADH 1 mutant displayed a greater ability to penetrate the EHOM
layers, one mechanism of action of ADH 1p in biofi lm formation may thus
be to modulate host tissue invasion by the Candida biofi lm. This aspect of
ADH1p's action in Candida biofi lm formation remains to be investigated
but will no doubt shed light on the use of an alternative treatment that
integrates the ADH1 gene/protein to overcome different forms of Candida
infection in humans.