Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins
Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhan...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00611/full |
| _version_ | 1818775086499364864 |
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| author | Manuela B. Pucca Manuela B. Pucca Shirin Ahmadi Shirin Ahmadi Felipe A. Cerni Felipe A. Cerni Line Ledsgaard Christoffer V. Sørensen Farrell T. S. McGeoghan Trenton Stewart Trenton Stewart Erwin Schoof Bruno Lomonte Ulrich auf dem Keller Eliane C. Arantes Figen Çalışkan Figen Çalışkan Andreas H. Laustsen |
| author_facet | Manuela B. Pucca Manuela B. Pucca Shirin Ahmadi Shirin Ahmadi Felipe A. Cerni Felipe A. Cerni Line Ledsgaard Christoffer V. Sørensen Farrell T. S. McGeoghan Trenton Stewart Trenton Stewart Erwin Schoof Bruno Lomonte Ulrich auf dem Keller Eliane C. Arantes Figen Çalışkan Figen Çalışkan Andreas H. Laustsen |
| author_sort | Manuela B. Pucca |
| collection | DOAJ |
| description | Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A2 from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA2 combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA2 complex formation. |
| first_indexed | 2024-12-18T10:51:27Z |
| format | Article |
| id | doaj.art-f708fbc151bd4462b01ad31680dc485f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-18T10:51:27Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f708fbc151bd4462b01ad31680dc485f2022-12-21T21:10:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00611520232Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and CytotoxinsManuela B. Pucca0Manuela B. Pucca1Shirin Ahmadi2Shirin Ahmadi3Felipe A. Cerni4Felipe A. Cerni5Line Ledsgaard6Christoffer V. Sørensen7Farrell T. S. McGeoghan8Trenton Stewart9Trenton Stewart10Erwin Schoof11Bruno Lomonte12Ulrich auf dem Keller13Eliane C. Arantes14Figen Çalışkan15Figen Çalışkan16Andreas H. Laustsen17Medical School, Federal University of Roraima, Boa Vista, BrazilDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biosafety, Graduate School of Natural and Applied Sciences, Eskişehir Osmangazi University, Eskişehir, TurkeyDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biology, Lund University, Lund, SwedenDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkFacultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa RicaDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Biotechnology and Biosafety, Graduate School of Natural and Applied Sciences, Eskişehir Osmangazi University, Eskişehir, TurkeyDepartment of Biology, Faculty of Science and Art, Eskişehir Osmangazi University, Eskişehir, TurkeyDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkToxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A2 from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA2 combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA2 complex formation.https://www.frontiersin.org/article/10.3389/fphar.2020.00611/fulltoxin synergismphospholipase A2toxin complexescytotoxinsmelittincytotoxicity |
| spellingShingle | Manuela B. Pucca Manuela B. Pucca Shirin Ahmadi Shirin Ahmadi Felipe A. Cerni Felipe A. Cerni Line Ledsgaard Christoffer V. Sørensen Farrell T. S. McGeoghan Trenton Stewart Trenton Stewart Erwin Schoof Bruno Lomonte Ulrich auf dem Keller Eliane C. Arantes Figen Çalışkan Figen Çalışkan Andreas H. Laustsen Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins Frontiers in Pharmacology toxin synergism phospholipase A2 toxin complexes cytotoxins melittin cytotoxicity |
| title | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins |
| title_full | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins |
| title_fullStr | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins |
| title_full_unstemmed | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins |
| title_short | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins |
| title_sort | unity makes strength exploring intraspecies and interspecies toxin synergism between phospholipases a2 and cytotoxins |
| topic | toxin synergism phospholipase A2 toxin complexes cytotoxins melittin cytotoxicity |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00611/full |
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