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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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 |
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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 |
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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 |
_version_ |
1743107050907369472 |
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13.18916 |