Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> 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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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/2/47 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Prateeksha |
| collection | DOAJ |
| 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 <i>Candida albicans</i> 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 <i>C</i>. <i>albicans</i> infections. |
| first_indexed | 2024-04-12T21:51:03Z |
| format | Article |
| id | doaj.art-b4851cde8eaf44189f037a2b425d4ed9 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-12T21:51:03Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b4851cde8eaf44189f037a2b425d4ed92022-12-22T03:15:30ZengMDPI AGBiomolecules2218-273X2019-01-01924710.3390/biom9020047biom9020047Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras SignalingPrateeksha0Braj Raj Singh1Vijai Kumar Gupta2Farah Deeba3Rajesh Bajpai4Vivek Pandey5Alim H. Naqvi6Dalip Kumar Upreti7Nicholas Gathergood8Yueming Jiang9Hesham A. El Enshasy10Essam Nageh Sholkamy11Ashraf A. Mostafa12Abd El-Latif Hesham13Brahma N. Singh14Herbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaCentre of Excellence in Materials Science (Nanomaterials), Z.H. College of Engineering and Technology, Aligarh Muslim University, Aligarh 202002, IndiaERA Chair of Green Chemistry, Department of Chemistry and Biotechnology, Tallinn University of Technology (TUT), 12618 Tallinn, EstoniaPlant Ecology and Climate Change Science Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaLichenology Laboratory, Plant Biodiversity and Conservation Biology Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaPlant Ecology and Climate Change Science Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaCentre of Excellence in Materials Science (Nanomaterials), Z.H. College of Engineering and Technology, Aligarh Muslim University, Aligarh 202002, IndiaLichenology Laboratory, Plant Biodiversity and Conservation Biology Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaERA Chair of Green Chemistry, Department of Chemistry and Biotechnology, Tallinn University of Technology (TUT), 12618 Tallinn, EstoniaKey Laboratory of Plant Resource Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, ChinaInstitute of Bioproduct Development, Universiti Teknologi Malaysia, Johor Bahru 81310, MalaysiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaMeta-Genome Biotechnology, Genetics Department, Faculty of Agriculture, Assiut University, Assiut 71526, EgyptHerbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow 226001, IndiaSilver-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 <i>Candida albicans</i> 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 <i>C</i>. <i>albicans</i> infections.https://www.mdpi.com/2218-273X/9/2/47fluconazole-resistant <i>Candida albicans</i>biosilver nanoclustersapoptosisRas signaling pathwayoxidative stressproteomics |
| spellingShingle | 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 Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling Biomolecules fluconazole-resistant <i>Candida albicans</i> biosilver nanoclusters apoptosis Ras signaling pathway oxidative stress proteomics |
| title | Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling |
| title_full | Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling |
| title_fullStr | Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling |
| title_full_unstemmed | Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling |
| title_short | Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant <i>Candida albicans</i> via Ras Signaling |
| title_sort | non toxic and ultra small biosilver nanoclusters trigger apoptotic cell death in fluconazole resistant i candida albicans i via ras signaling |
| topic | fluconazole-resistant <i>Candida albicans</i> biosilver nanoclusters apoptosis Ras signaling pathway oxidative stress proteomics |
| url | https://www.mdpi.com/2218-273X/9/2/47 |
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