Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins

Author(s):Show less -

Pucca, Manuela B. ^{[1, 2]} ; Ahmadi, Shirin ^{[1, 3]} ; Cerni, Felipe A. ^{[1, 4]} ; Ledsgaard, Line ^[1] ; Sorensen, V, Christoffer ; McGeoghan, Farrell T. S. ^[5] ; Stewart, Trenton ^{[6, 5]} ; Schoof, Erwin ^[5] ; Lomonte, Bruno ^[7] ; Keller, Ulrich auf dem ^[5] ; Arantes, Eliane C. ^[4] ; Caliskan, Figen ^{[3, 8]} ; Laustsen, Andreas H. ^[5]

Affiliation

^[1] Tech Univ Denmark, Dept Biotechnol & Biomed, Lyngby - Denmark

^[2] Univ Fed Roraima, Med Sch, Boa Vista, Parana - Brazil

^[3] Eskisehir Osmangazi Univ, Grad Sch Nat & Appl Sci, Dept Biotechnol & Biosafety, Eskisehir - Turkey

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept BioMol Sci, Ribeirao Preto - Brazil

^[5] Sorensen, Christoffer, V, Tech Univ Denmark, Dept Biotechnol & Biomed, Lyngby - Denmark

^[6] Lund Univ, Dept Biol, Lund - Sweden

^[7] Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose - Costa Rica

^[8] Eskisehir Osmangazi Univ, Fac Sci & Art, Dept Biol, Eskisehir - Turkey

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 11, MAY 7 2020.
• Web of Science Citations: 0

Abstract

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 A(2) 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-PLA(2) 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 PLA(2) complex formation. (AU)

• FAPESP's process: 17/04724-4 - Improving of human fragment antibodies (scFVs) specific for animals' venoms
• Grantee: Eliane Candiani Arantes Braga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/14035-1 - Improving of human fragment antibodies (scFvs) specific for animals' venoms
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/14158-9 - Improving of human fragment antibodies (scFvs) specific for animals' venoms
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor