Non-toxic and ultra-small biosilver nanoclusters trigger apoptotic cell death in fluconazole-resistant Candida albicans via Ras signaling

Prateeksha, Braj Raj Singh, Vijai Kumar Gupta*, Farah Deeba, Rajesh Bajpai, Vivek Pandey, Alim H. Naqvi, Dalip Kumar Upreti, Nicholas Gathergood, Yueming Jiang, Hesham A. El Enshasy, Essam Nageh Sholkamy, Ashraf A. Mostafa, Abd El Latif Hesham, Brahma N. Singh

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Silver-based nanostructures are suitable for many biomedical applications, but to be useful therapeutic agents, the high toxicity of these nanomaterials must be eliminated. Here, we biosynthesize nontoxic and ultra-small silver nanoclusters (rsAg@NCs) using metabolites of usnioid lichen (a symbiotic association of algae and fungi) that exhibit excellent antimicrobial activity against fluconazole (FCZ)-resistant Candida albicans that is many times higher than chemically synthesized silver nanoparticles (AgNPs) and FCZ. The rsAg@NCs trigger apoptosis via reactive oxygen species accumulation that leads to the loss of mitochondrial membrane potential, DNA fragmentation, chromosomal condensation, and the activation of metacaspases. The proteomic analysis clearly demonstrates that rsAg@NCs exposure significantly alters protein expression. Most remarkable among the down-regulated proteins are those related to glycolysis, metabolism, free radical scavenging, anti-apoptosis, and mitochondrial function. In contrast, proteins involved in plasma membrane function, oxidative stress, cell death, and apoptosis were upregulated. Eventually, we also established that the apoptosis-inducing potential of rsAg@NCs is due to the activation of Ras signaling, which confirms their application in combating FCZ-resistant C. albicans infections.

Original languageEnglish
Article number47
JournalBiomolecules
Volume9
Issue number2
Early online date29 Jan 2019
DOIs
Publication statusPrint publication - 1 Feb 2019
Externally publishedYes

Keywords

  • Apoptosis
  • Biosilver nanoclusters
  • Fluconazole-resistant Candida albicans
  • Oxidative stress
  • Proteomics
  • Ras signaling pathway

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    Prateeksha, Singh, B. R., Gupta, V. K., Deeba, F., Bajpai, R., Pandey, V., Naqvi, A. H., Upreti, D. K., Gathergood, N., Jiang, Y., El Enshasy, H. A., Sholkamy, E. N., Mostafa, A. A., Hesham, A. E. L., & Singh, B. N. (2019). Non-toxic and ultra-small biosilver nanoclusters trigger apoptotic cell death in fluconazole-resistant Candida albicans via Ras signaling. Biomolecules, 9(2), [47]. https://doi.org/10.3390/biom9020047