Toxicity
challenges by antifungal arsenals and emergence of multidrug
resistance scenario has posed a serious threat to global community.
To cope up with this alarming situation, phytoactive molecules are
richest, safest, and most effective source of broad spectrum antimicrobial
compounds. In the present investigation, six phytoactive molecules
[cinnamaldehyde (CIN), epigallocatechin, vanillin, eugenol (EUG),
furanone, and epigallocatechin gallate] were studied against
Candida glabrata
and its clinical isolates. Among
these, CIN and EUG which are active components of cinnamon and clove
essential oils, respectively, exhibited maximum inhibition against
planktonic growth of
C. glabrata
at
a concentration of 64 and 128 μg mL
–1
, respectively.
These two molecules effectively inhibited and eradicated approximately
80% biofilm of
C. glabrata
and its
clinical isolates from biomaterials. CIN and EUG increased reactive
oxygen species generation, cell lysis, and ergosterol content in plasma
membrane and reduced virulence attributes (phospholipase and proteinase)
as well as catalase activity of
C. glabrata
cells. Reduction of mitochondrial membrane potential with increased
release of cytochrome
c
from mitochondria to cytosol
indicated initiation of early apoptosis in CIN- and EUG-treated
C. glabrata
cells. Transcriptional analysis showed
that multidrug transporter (
CDR1
) and ergosterol
biosynthesis genes were downregulated in the presence of CIN, while
getting upregulated in EUG-treated cells. Interestingly, genes such
as 1,3-β-glucan synthase (
FKS1
), GPI-anchored
protein (
KRE1
), and sterol importer (
AUS1
) were downregulated upon treatment of CIN/EUG. These results provided
molecular-level insights about the antifungal mechanism of CIN and
EUG against
C. glabrata
including its
resistant clinical isolate. The current data established that CIN
and EUG can be potentially formulated in new antifungal strategies.