The Journal of Antibiotics
https://doi.org/10.1038/s41429-019-0185-9
BRIEF COMMUNICATION
Molecular targets of biofabricated silver nanoparticles in Candida
albicans
Shivkrupa D. Halbandge
1
●
Ashwini K. Jadhav
2
●
Priyanka M. Jangid
1
●
Amruta V. Shelar
3,4
●
Rajendra H. Patil
3
●
Sankunny Mohan Karuppayil
1
Received: 19 January 2019 / Revised: 7 March 2019 / Accepted: 25 March 2019
© The Author(s), under exclusive licence to the Japan Antibiotics Research Association 2019
Abstract
We have analyzed the expressions of genes which regulate Ras-cAMP-EFG1 and CEK1-MAPK pathways involved in yeast
to hyphal form morphogenesis in Candida albicans. The expression profile of genes associated with serum-induced
morphogenesis showed reduced expressions of genes involved in these pathways by the treatment with biofabricated silver
nanoparticles. Cell elongation gene, ECE1, was downregulated by 5.1 fold by the treatment of silver nanoparticles.
Expression of hyphal inducer gene, TEC1 was downregulated by 6.28 fold. Negative regulators of yeast to hyphal transition,
TUP1 and RFG1 were downregulated by 2.45 and 5.43 fold, respectively. Current study suggests that silver nanoparticles
affect gene expression and may subsequently reduce virulence in C. albicans. Targeting genes involved in virulence may be
an acceptable novel treatment strategy for pathogenic fungal infections.
Introduction
Candida albicans is considered as a major fungal pathogen
of the humans causing considerable morbidity and mortal-
ity. Currently prescribed antifungal antibiotics are often
failures in clinical situations, due to the development of
multiple drug resistance, formation of drug resistant bio-
films on biotic as well as abiotic surfaces and transformation
from yeast to hyphal (Y-H) form morphology [1]. This has
resulted in the use of higher dosages of antibiotics and
prolonged therapy which may result in undesirable side
effects to the patients [2]. There is a need to find alternative
therapy which is free from side effects. There is consider-
able interest in using nanotechnology-based drugs [3]. The
targets of silver nanoparticles in C. albicans include: cell
wall, cell membrane, mitochondrial function, changes in
membrane fluidity, changes in fatty acids, inhibition of
ergosterol synthesis, formation Reactive oxygen species,
release of silver ions, ultra structural changes, apoptosis,
cell cycle arrest etc. [4]. Silver nanoparticles (SNPs) have
been shown to inhibit the expression of genes involved drug
efflux in drug resistant clinical isolates [5]. As Y-H form
morphogenesis is one of the major virulence factors in C.
albicans and necessary for penetrating the epithelial tissues
and escape from immune response [6]. Y-H form transition
involves two signaling pathways, Ras1-cAMP-PKA and
Cek1-MAPK pathway [6]. Targeting of hyphal specific
genes involved in these pathways may be a promising
strategy for anticandida drug development [7].We are pre-
senting information on the downregulation of genes
involved in Y-H signal transduction in C. albicans after the
treatment of SNPs. This is the first report on SNPs targeting
signal transduction in C. albicans.
Materials and methods
Synthesis of SNPs
Silver nitrate (AgNO
3
) was procured from Himedia Che-
micals Ltd, Mumbai, India. Silver nitrate solution (1 mM)
* Sankunny Mohan Karuppayil
prof.karuppayil@gmail.com
1
School of Life Sciences, SRTM University, Nanded, Maharashtra
431606, India
2
Department of Stem Cell and Regenerative medicine, Centre For
Interdisciplinary Research, DY Patil Education Society (Deemed
to be University), Kolhapur, Maharashtra 416006, India
3
Department of Biotechnology, Savitribai Phule, Pune University,
Ganeshkhind, Pune, Maharashtra 411007, India
4
Department of Technology, Savitribai Phule, Pune University,
Ganeshkhind, Pune, Maharashtra 411007, India
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