Amity Institute of Biotechnology, Amity University, Haryana, Gurgaon (Manesar) -122413, India
Candida albicans is known to cause infections ranging from superficial
and systemic in immunocompromised person. In this study, we explored that the
antifungal action of Methylene blue (MB) is mediated through mitochondrial
dysfunction and disruption of redox and membrane homeostasis against C.
albicans. We demonstrated that MB displayed its antifungal potential against
C. albicans and two clinical isolates tested. We also showed that MB is
effective against two non- albicans species as well. Notably, the
antifungal effect of MB seems to be independent of the major drug efflux pumps
transporter activity. We explored that MB treated Candida cells were
sensitive on non-fermentable carbon source leading us to propose that MB
inhibits mitochondria. This sensitive phenotype was reinforced with the fact
that sensitivity of Candida cells to MB could be rescued upon the
supplementation of ascorbic acid, an antioxidant. This clearly suggests that
disturbances in redox status are linked with MB action. We further demonstrated
that Candida cells were susceptible to membrane perturbing agent viz. SDS
which was additionally confirmed by transmission electron micrographs showing
disruption of membrane integrity. Moreover, the ergosterol levels were
significantly decreased by 66% suggesting lipid compositional changes due to MB.
Furthermore, we could demonstrate that MB inhibits the yeast to hyphal
transition in C. albicans which is one of the major virulence attribute
in most of the hyphal inducing conditions. Taken together, the data generated
from present study clearly establishes MB as promising antifungal agent that
could be efficiently employed in strategies to treat Candida infections.
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firstname.lastname@example.org#Both authors contributed equally to this work.