Application of Venom Phospholipase in the Treatment of Diseases

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 14735

Special Issue Editor

Department of Physiology, Kyung Hee University, Seoul, South Korea
Interests: venom phospholipase identification and characterization; venom phospholipase efficacy evaluation; mode of action of phospholipases; structure–function relationship of phospholipases; venom phospholipase as a drug development process; clinical application of venom phospholipases

Special Issue Information

Venom phospholipases consist of hydrolase classes that catalyze the hydrolysis of acyl esters and phosphate esters on phospholipids. The phospholipases A2s are among the most studied ones, as they have been known for over a century from research on snake and bee venom, and many mechanistic studies have been carried out on their numerous isoforms. Besides phospholipase A2 of snake and bee venom, many kinds of phospholipases have been identified in venoms. For example, the venoms of Australian elapid snake, cobra, and brown spider contain phospholipase B, C, and D, respectively.  Phospholipase-like proteins with toxic properties, yet which lack a functional catalytic site, are also found in venoms.

Phospholipases, major digestive enzymes present in venoms, play a critical role in many physiological processes including the generation and aggregation of numerous signaling lipids. In addition, they seem to affect various diseases in some manner. This Special Issue aims to provide a comprehensive view on venom phospholipases, including their characterization, function, and mechanism of action in the treatment of various diseases.

Prof. Dr. Hyunsu Bae
Guest Editor

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Keywords

  • phospholipase
  • phospholipase A2
  • venom
  • disease
  • therapy
  • drug

Published Papers (5 papers)

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Research

13 pages, 2966 KiB  
Article
Bee Venom Phospholipase A2 Ameliorates Atherosclerosis by Modulating Regulatory T Cells
by Geun-Hyung Kang, Sujin Lee, Da Bin Choi, Dasom Shin, Jahee Kim, HyeJin Yang and Hyunsu Bae
Toxins 2020, 12(10), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100609 - 23 Sep 2020
Cited by 7 | Viewed by 3098
Abstract
Atherosclerosis is a chronic inflammatory disease caused by lipids and calcareous accumulations in the vascular wall due to an inflammatory reaction. Recent reports have demonstrated that regulatory T (Treg) cells have an important role as a new treatment for atherosclerosis. This study suggests [...] Read more.
Atherosclerosis is a chronic inflammatory disease caused by lipids and calcareous accumulations in the vascular wall due to an inflammatory reaction. Recent reports have demonstrated that regulatory T (Treg) cells have an important role as a new treatment for atherosclerosis. This study suggests that bee venom phospholipase A2 (bvPLA2) may be a potential therapeutic agent in atherosclerosis by inducing Treg cells. We examined the effects of bvPLA2 on atherosclerosis using ApoE-/- and ApoE-/-/Foxp3DTR mice. In this study, bvPLA2 increased Treg cells, followed by a decrease in lipid accumulation in the aorta and aortic valve and the formation of foam cells. Importantly, the effect of bvPLA2 was found to depend on Treg cells. This study suggests that bvPLA2 can be a potential therapeutic agent for atherosclerosis. Full article
(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)
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15 pages, 1159 KiB  
Article
Antibiofilm Activity of Acidic Phospholipase Isoform Isolated from Bothrops erythromelas Snake Venom
by Ellynes Nunes, Breno Frihling, Elizângela Barros, Caio de Oliveira, Newton Verbisck, Taylla Flores, Augusto de Freitas Júnior, Octávio Franco, Maria de Macedo, Ludovico Migliolo and Karla Luna
Toxins 2020, 12(9), 606; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090606 - 20 Sep 2020
Cited by 7 | Viewed by 3122
Abstract
Introduction: Bacterial resistance is a worldwide public health problem, requiring new therapeutic options. An alternative approach to this problem is the use of animal toxins isolated from snake venom, such as phospholipases A2 (PLA2), which have important antimicrobial activities. Bothrops [...] Read more.
Introduction: Bacterial resistance is a worldwide public health problem, requiring new therapeutic options. An alternative approach to this problem is the use of animal toxins isolated from snake venom, such as phospholipases A2 (PLA2), which have important antimicrobial activities. Bothropserythromelas is one of the snake species in the northeast of Brazil that attracts great medical-scientific interest. Here, we aimed to purify and characterize a PLA2 from B. erythromelas, searching for heterologous activities against bacterial biofilms. Methods: Venom extraction and quantification were followed by reverse-phase high-performance liquid chromatography (RP-HPLC) in C18 column, matrix-assisted ionization time-of-flight (MALDI-ToF) mass spectrometry, and sequencing by Edman degradation. All experiments were monitored by specific activity using a 4-nitro-3-(octanoyloxy) benzoic acid (4N3OBA) substrate. In addition, hemolytic tests and antibacterial tests including action against Escherichiacoli, Staphylococcusaureus, and Acinetobacterbaumannii were carried out. Moreover, tests of antibiofilm action against A. baumannii were also performed. Results: PLA2, after one purification step, presented 31 N-terminal amino acid residues and a molecular weight of 13.6564 Da, with enzymatic activity confirmed in 0.06 µM concentration. Antibacterial activity against S. aureus (IC50 = 30.2 µM) and antibiofilm activity against A. baumannii (IC50 = 1.1 µM) were observed. Conclusions: This is the first time that PLA2 purified from B. erythromelas venom has appeared as an alternative candidate in studies of new antibacterial medicines. Full article
(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)
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17 pages, 4151 KiB  
Article
Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms
by Amanda Pissinatti Canelli, Taís Fernanda dos Santos Rodrigues, Vivian Fernandes Furletti de Goes, Guilherme Ferreira Caetano and Maurício Ventura Mazzi
Toxins 2020, 12(9), 532; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090532 - 20 Aug 2020
Cited by 8 | Viewed by 2422
Abstract
The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules [...] Read more.
The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules derived from natural products. Herein, crotoxin (CTX), the main toxin of Crotalus durissus terrificus venom, was challenged against Candida tropicalis (CBS94) and Candida dubliniensis (CBS7987) strains by in vitro antimicrobial susceptibility tests. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and inhibition of biofilm formation were evaluated after CTX treatment. In addition, CTX-induced cytotoxicity in HaCaT cells was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. Native CTX showed a higher antimicrobial activity (MIC = 47 μg/mL) when compared to CTX-containing mouthwash (MIC = 750 μg/mL) and nystatin (MIC = 375 μg/mL). Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 μg/mL) when compared to nystatin (IC100 > 47 μg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains. Full article
(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)
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14 pages, 6078 KiB  
Article
A Role of Newly Found Auxiliary Site in Phospholipase A1 from Thai Banded Tiger Wasp (Vespa affinis) in Its Enzymatic Enhancement: In Silico Homology Modeling and Molecular Dynamics Insights
by Withan Teajaroen, Suphaporn Phimwapi, Jureerut Daduang, Sompong Klaynongsruang, Varomyalin Tipmanee and Sakda Daduang
Toxins 2020, 12(8), 510; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12080510 - 08 Aug 2020
Cited by 8 | Viewed by 2980
Abstract
Phospholipase A1 from Thai banded tiger wasp (Vespa affinis) venom also known as Ves a 1 plays an essential role in fatal vespid allergy. Ves a 1 becomes an important therapeutic target for toxin remedy. However, established Ves a 1 structure or [...] Read more.
Phospholipase A1 from Thai banded tiger wasp (Vespa affinis) venom also known as Ves a 1 plays an essential role in fatal vespid allergy. Ves a 1 becomes an important therapeutic target for toxin remedy. However, established Ves a 1 structure or a mechanism of Ves a 1 function were not well documented. This circumstance has prevented efficient design of a potential phospholipase A1 inhibitor. In our study, we successfully recruited homology modeling and molecular dynamic (MD) simulation to model Ves a 1 three-dimensional structure. The Ves a 1 structure along with dynamic behaviors were visualized and explained. In addition, we performed molecular docking of Ves a 1 with 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) lipid to assess a possible lipid binding site. Interestingly, molecular docking predicted another lipid binding region apart from its corresponding catalytic site, suggesting an auxiliary role of the alternative site at the Ves a 1 surface. The new molecular mechanism related to the surface lipid binding site (auxiliary site) provided better understanding of how phospholipase A1 structure facilitates its enzymatic function. This auxiliary site, conserved among Hymenoptera species as well as some mammalian lipases, could be a guide for interaction-based design of a novel phospholipase A1 inhibitor. Full article
(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)
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12 pages, 2286 KiB  
Communication
Functional Profile of Antigen Specific CD4+ T Cells in the Immune Response to Phospholipase A1 Allergen from Polybia paulista Venom
by Luís Gustavo Romani Fernandes, Amilcar Perez-Riverol, Murilo Luiz Bazon, Débora Moitinho Abram, Márcia Regina Brochetto-Braga and Ricardo de Lima Zollner
Toxins 2020, 12(6), 379; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12060379 - 08 Jun 2020
Cited by 3 | Viewed by 2613
Abstract
Insect venom can cause systemic allergic reactions, including anaphylaxis. Improvements in diagnosis and venom immunotherapy (VIT) are based on a better understanding of an immunological response triggered by venom allergens. Previously, we demonstrated that the recombinant phospholipase A1 (rPoly p 1) from Polybia [...] Read more.
Insect venom can cause systemic allergic reactions, including anaphylaxis. Improvements in diagnosis and venom immunotherapy (VIT) are based on a better understanding of an immunological response triggered by venom allergens. Previously, we demonstrated that the recombinant phospholipase A1 (rPoly p 1) from Polybia paulista wasp venom induces specific IgE and IgG antibodies in sensitized mice, which recognized the native allergen. Here, we addressed the T cell immune response of rPoly p 1-sensitized BALB/c mice. Cultures of splenocytes were stimulated with Polybia paulista venom extract and the proliferation of CD8+ and CD4+ T cells and the frequency of T regulatory cells (Tregs) populations were assessed by flow cytometry. Cytokines were quantified in cell culture supernatants in ELISA assays. The in vitro stimulation of T cells from sensitized mice induces a significant proliferation of CD4+ T cells, but not of CD8+ T cells. The cytokine pattern showed a high concentration of IFN-γ and IL-6, and no significant differences to IL-4, IL-1β and TGF-β1 production. In addition, the rPoly p 1 group showed a pronounced expansion of CD4+CD25+FoxP3+ and CD4+CD25-FoxP3+ Tregs. rPoly p 1 sensitization induces a Th1/Treg profile in CD4+ T cell subset, suggesting its potential use in wasp venom immunotherapy. Full article
(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)
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