NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING

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...

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Main Authors: Prateeksha, Prateeksha, Singh, Braj Raj, Gupta, Vijai Kumar, Deeba, Farah, Bajpai, Rajesh, Pandey, Vivek, Naqvi, Alim H., Upreti, Dalip Kumar, Gathergood, Nicholas, Jiang, Yueming, El Enshasy, Hesham A., Sholkamy, Essam Nageh, Mostafa, Ashraf A., Hesham, Abd. El-Latif, Singh, Brahma N.
Format: Article
Language:English
Published: MDPI AG 2019
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Online Access:http://eprints.utm.my/id/eprint/96955/1/HeshamAli2019_NonToxicandUltraSmallBiosilverNanoclusters.pdf
http://eprints.utm.my/id/eprint/96955/
http://dx.doi.org/10.3390/biom9020047
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spelling my.utm.969552022-09-04T07:52:19Z http://eprints.utm.my/id/eprint/96955/ NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING Prateeksha, Prateeksha Singh, Braj Raj Gupta, Vijai Kumar Deeba, Farah Bajpai, Rajesh Pandey, Vivek Naqvi, Alim H. Upreti, Dalip Kumar Gathergood, Nicholas Jiang, Yueming El Enshasy, Hesham A. Sholkamy, Essam Nageh Mostafa, Ashraf A. Hesham, Abd. El-Latif Singh, Brahma N. TP Chemical technology 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. MDPI AG 2019 Article PeerReviewed application/pdf en http://eprints.utm.my/id/eprint/96955/1/HeshamAli2019_NonToxicandUltraSmallBiosilverNanoclusters.pdf Prateeksha, Prateeksha and Singh, Braj Raj and Gupta, Vijai Kumar and Deeba, Farah and Bajpai, Rajesh and Pandey, Vivek and Naqvi, Alim H. and Upreti, Dalip Kumar and Gathergood, Nicholas and Jiang, Yueming and El Enshasy, Hesham A. and Sholkamy, Essam Nageh and Mostafa, Ashraf A. and Hesham, Abd. El-Latif and Singh, Brahma N. (2019) NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING. Biomolecules, 9 (2). pp. 1-23. ISSN 2218-273X http://dx.doi.org/10.3390/biom9020047 DOI : 10.3390/biom9020047
institution Universiti Teknologi Malaysia
building UTM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Teknologi Malaysia
content_source UTM Institutional Repository
url_provider http://eprints.utm.my/
language English
topic TP Chemical technology
spellingShingle TP Chemical technology
Prateeksha, Prateeksha
Singh, Braj Raj
Gupta, Vijai Kumar
Deeba, Farah
Bajpai, Rajesh
Pandey, Vivek
Naqvi, Alim H.
Upreti, Dalip Kumar
Gathergood, Nicholas
Jiang, Yueming
El Enshasy, Hesham A.
Sholkamy, Essam Nageh
Mostafa, Ashraf A.
Hesham, Abd. El-Latif
Singh, Brahma N.
NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
description 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.
format Article
author Prateeksha, Prateeksha
Singh, Braj Raj
Gupta, Vijai Kumar
Deeba, Farah
Bajpai, Rajesh
Pandey, Vivek
Naqvi, Alim H.
Upreti, Dalip Kumar
Gathergood, Nicholas
Jiang, Yueming
El Enshasy, Hesham A.
Sholkamy, Essam Nageh
Mostafa, Ashraf A.
Hesham, Abd. El-Latif
Singh, Brahma N.
author_facet Prateeksha, Prateeksha
Singh, Braj Raj
Gupta, Vijai Kumar
Deeba, Farah
Bajpai, Rajesh
Pandey, Vivek
Naqvi, Alim H.
Upreti, Dalip Kumar
Gathergood, Nicholas
Jiang, Yueming
El Enshasy, Hesham A.
Sholkamy, Essam Nageh
Mostafa, Ashraf A.
Hesham, Abd. El-Latif
Singh, Brahma N.
author_sort Prateeksha, Prateeksha
title NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
title_short NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
title_full NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
title_fullStr NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
title_full_unstemmed NON-TOXIC AND ULTRA-SMALL BIOSILVER NANOCLUSTERS TRIGGER APOPTOTIC CELL DEATH IN FLUCONAZOLE-RESISTANT CANDIDA ALBICANS VIA RAS SIGNALING
title_sort non-toxic and ultra-small biosilver nanoclusters trigger apoptotic cell death in fluconazole-resistant candida albicans via ras signaling
publisher MDPI AG
publishDate 2019
url http://eprints.utm.my/id/eprint/96955/1/HeshamAli2019_NonToxicandUltraSmallBiosilverNanoclusters.pdf
http://eprints.utm.my/id/eprint/96955/
http://dx.doi.org/10.3390/biom9020047
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