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1.
PLoS One ; 18(1): e0277303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649362

RESUMO

Scorpions represent an ancient lineage of arachnids that have radiated across the globe and are incredibly resilient-since some thrive in harsh environments and can exist on minimal and intermittent feedings. Given the emerging importance of microbiomes to an organism's health, it is intriguing to suggest that the long-term success of the scorpion bauplan may be linked to the microbiome. Little is known about scorpion microbiomes, and what is known, concentrates on the gut. The microbiome is not limited to the gut, rather it can be found within tissues, fluids and on external surfaces. We tested whether the scorpion telson, the venom-producing organ, of two species, Smeringurus mesaensis and Hadrurus arizonensis, contain bacteria. We isolated telson DNA from each species, amplified bacterial 16S rRNA genes, and identified the collection of bacteria present within each scorpion species. Our results show for the first time that telsons of non-buthid scorpion species do indeed contain bacteria. Interestingly, each scorpion species has a phylogenetically unique telson microbiome including Mollicutes symbionts. This study may change how we view scorpion biology and their venoms.


Assuntos
Venenos de Escorpião , Tenericutes , Animais , Escorpiões/genética , Escorpiões/microbiologia , RNA Ribossômico 16S/genética , Peçonhas , Bactérias/genética , Tenericutes/genética , Venenos de Escorpião/genética
2.
Toxins (Basel) ; 15(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36668897

RESUMO

Patients bitten by Protobothrops mucrosquamatus, Viridovipera stejnegeri, and Naja atra develop different degrees of wound infection. This study validated BITE and Cobra BITE scoring systems that we established previously. Bacteriological studies of patients with wound infection were conducted. The operating characteristic curves and area under the curve (AUC) and wound infection rates were compared between the derivation set (our previous study patient population) and the validation set (new patient cohorts enrolled between June 2017 and May 2021). No significant differences in the AUC for both the BITE (0.84 vs. 0.78, p = 0.27) and Cobra BITE (0.88 vs. 0.75, p = 0.21) scoring systems were observed between the derivation and validation sets. Morganella morganii and Enterococcus faecalis were the two most commonly detected bacteria in the microbiological study. More bacterial species were cultured from N. atra-infected wounds. Antibiotics such as amoxicillin with clavulanic acid, oxacillin, and ampicillin may not be suitable for treating patients with P. mucrosquamatus, V. stejnegeri, and N. atra bites in Taiwan. Carbapenem, third-generation cephalosporins, and fluoroquinolone may be superior alternatives.


Assuntos
Mordeduras de Serpentes , Infecção dos Ferimentos , Animais , Humanos , Mordeduras de Serpentes/terapia , Elapidae , Naja naja , Peçonhas , Taiwan/epidemiologia , Bactérias , Infecção dos Ferimentos/tratamento farmacológico , Venenos Elapídicos , Antivenenos
3.
BMC Biol ; 21(1): 5, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617555

RESUMO

BACKGROUND: Eusociality is widely considered to evolve through kin selection, where the reproductive success of an individual's close relative is favored at the expense of its own. High genetic relatedness is thus considered a prerequisite for eusociality. While ants are textbook examples of eusocial animals, not all ants form colonies of closely related individuals. One such example is the ectatommine ant Rhytidoponera metallica, which predominantly forms queen-less colonies that have such a low intra-colony relatedness that they have been proposed to represent a transient, unstable form of eusociality. However, R. metallica is among the most abundant and widespread ants on the Australian continent. This apparent contradiction provides an example of how inclusive fitness may not by itself explain the maintenance of eusociality and raises the question of what other selective advantages maintain the eusocial lifestyle of this species. RESULTS: We provide a comprehensive portrait of the venom of R. metallica and show that the colony-wide venom consists of an exceptionally high diversity of functionally distinct toxins for an ant. These toxins have evolved under strong positive selection, which is normally expected to reduce genetic variance. Yet, R. metallica exhibits remarkable intra-colony variation, with workers sharing only a relatively small proportion of toxins in their venoms. This variation is not due to the presence of chemical castes, but has a genetic foundation that is at least in part explained by toxin allelic diversity. CONCLUSIONS: Taken together, our results suggest that the toxin diversity contained in R. metallica colonies may be maintained by a form of group selection that selects for colonies that can exploit more resources and defend against a wider range of predators. We propose that increased intra-colony genetic variance resulting from low kinship may itself provide a selective advantage in the form of an expanded pharmacological venom repertoire. These findings provide an example of how group selection on adaptive phenotypes may contribute to maintaining eusociality where a prerequisite for kin selection is diminished.


Assuntos
Formigas , Animais , Formigas/genética , Peçonhas , Austrália , Reprodução , Comportamento Social
4.
Toxicon ; 223: 107012, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592762

RESUMO

The methylotrophic yeast Pichia pastoris has been one of the most widely used organisms in recent years as an expression system for a wide variety of recombinant proteins with therapeutic potential. Its popularity as an alternative system to Escherichia coli is mainly due to the easy genetic manipulation and the ability to produce high levels of heterologous proteins, either intracellularly or extracellularly. Being a eukaryotic organism, P. pastoris carries out post-translational modifications that allow it to produce soluble and correctly folded recombinant proteins. This work, evaluated the expression capacity in P. pastoris of two single-chain variable fragments (scFvs) of human origin, 10FG2 and LR. These scFvs were previously obtained by directed evolution against scorpion venom toxins and are able to neutralize different toxins and venoms of Mexican species. The yield obtained in P. pastoris was higher than that obtained in bacterial periplasm (E. coli), and most importantly, biochemical and functional properties were not modified. These results confirm that P. pastoris yeast can be a good expression system for the production of antibody fragments of a new recombinant antivenom.


Assuntos
Escorpiões , Peçonhas , Animais , Humanos , Escorpiões/química , Peçonhas/metabolismo , Saccharomyces cerevisiae/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes/química , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/metabolismo
5.
Toxicon ; 223: 107006, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36572114

RESUMO

The genus Odontomachus is widely distributed in neotropical areas throughout Central and South America. It is a stinging ant that subdues its prey (insects) by injecting them a cocktail of toxic molecules (venom). Ant venoms are generally composed of formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Odontomachus chelifer is an ant that inhabits neotropical regions from Mexico to Argentina. Unlike the venom of other animals such as scorpions, spiders and snakes, this ant venom has seldom been analyzed comprehensively, and their compositions are not yet completely known. In the present study, we performed a partial investigation of enzymatic and functional activities of O. chelifer ant venom, and we provide a global insight on the transcripts expressed in the venom gland to better understand their properties. The crude venom showed phospholipase A2 and antiparasitic activities. RNA sequencing (Illumina platform) of the venom gland of O. chelifer generated 61, 422, 898 reads and de novo assembly Trinity generated 50,220 contigs. BUSCO analysis against Arthropoda_db10 showed that 92.89% of the BUSCO groups have complete gene representation (single-copy or duplicated), while 4.05% are only partially recovered, and 3.06% are missing. The 30 most expressed genes in O. chelifer venom gland transcriptome included important transcripts involved in venom function such as U-poneritoxin (01)-Om1a-like (pilosulin), chitinase 2, venom allergen 3, chymotrypsin 1 and 2 and glutathione S-transferase. Analysis of the molecular function revealed that the largest number of transcripts were related to catalytic activity, including phospholipases. These data emphasize the potential of O. chelifer venom for prospection of molecules with biotechnological application.


Assuntos
Venenos de Formiga , Formigas , Animais , Transcriptoma , Formigas/genética , Venenos de Formiga/genética , Venenos de Formiga/química , Perfilação da Expressão Gênica , Peptídeos/análise , Peçonhas/metabolismo , Alérgenos
6.
Mar Drugs ; 20(12)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36547910

RESUMO

Complex pathological diseases, such as cancer, infection, and Alzheimer's, need to be targeted by multipronged curative. Various omics technologies, with a high rate of data generation, demand artificial intelligence to translate these data into druggable targets. In this study, 82 marine venomous animal species were retrieved, and 3505 cryptic cell-penetrating peptides (CPPs) were identified in their toxins. A total of 279 safe peptides were further analyzed for antimicrobial, anticancer, and immunomodulatory characteristics. Protease-resistant CPPs with endosomal-escape ability in Hydrophis hardwickii, nuclear-localizing peptides in Scorpaena plumieri, and mitochondrial-targeting peptides from Synanceia horrida were suitable for compartmental drug delivery. A broad-spectrum S. horrida-derived antimicrobial peptide with a high binding-affinity to bacterial membranes was an antigen-presenting cell (APC) stimulator that primes cytokine release and naïve T-cell maturation simultaneously. While antibiofilm and wound-healing peptides were detected in Synanceia verrucosa, APC epitopes as universal adjuvants for antiviral vaccination were in Pterois volitans and Conus monile. Conus pennaceus-derived anticancer peptides showed antiangiogenic and IL-2-inducing properties with moderate BBB-permeation and were defined to be a tumor-homing peptide (THP) with the ability to inhibit programmed death ligand-1 (PDL-1). Isoforms of RGD-containing peptides with innate antiangiogenic characteristics were in Conus tessulatus for tumor targeting. Inhibitors of neuropilin-1 in C. pennaceus are proposed for imaging probes or therapeutic delivery. A Conus betulinus cryptic peptide, with BBB-permeation, mitochondrial-targeting, and antioxidant capacity, was a stimulator of anti-inflammatory cytokines and non-inducer of proinflammation proposed for Alzheimer's. Conclusively, we have considered the dynamic interaction of cells, their microenvironment, and proportional-orchestrating-host- immune pathways by multi-target-directed CPPs resembling single-molecule polypharmacology. This strategy might fill the therapeutic gap in complex resistant disorders and increase the candidates' clinical-translation chance.


Assuntos
Doença de Alzheimer , Anti-Infecciosos , Peptídeos Penetradores de Células , Neoplasias , Animais , Peptídeos Penetradores de Células/farmacologia , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/uso terapêutico , Peçonhas , Inteligência Artificial , Polifarmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral
7.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36499761

RESUMO

Peptides are potential therapeutic alternatives against global diseases, such as antimicrobial-resistant infections and cancer. Venoms are a rich source of bioactive peptides that have evolved over time to act on specific targets of the prey. Peptides are one of the main components responsible for the biological activity and toxicity of venoms. South American organisms such as scorpions, snakes, and spiders are important producers of a myriad of peptides with different biological activities. In this review, we report the main venom-derived peptide families produced from South American organisms and their corresponding activities and biological targets.


Assuntos
Neoplasias , Peçonhas , Animais , Peçonhas/farmacologia , Peçonhas/uso terapêutico , Escorpiões/química , Peptídeos/farmacologia , Peptídeos/química , Neoplasias/tratamento farmacológico , Resistência Microbiana a Medicamentos
8.
Toxins (Basel) ; 14(12)2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36548740

RESUMO

The evolution of venom and the selection pressures that act on toxins have been increasingly researched within toxinology in the last two decades, in part due to the exceptionally high rates of diversifying selection observed in animal toxins. In 2015, Sungar and Moran proposed the 'two-speed' model of toxin evolution linking evolutionary age of a group to the rates of selection acting on toxins but due to a lack of data, mammals were not included as less than 30 species of venomous mammal have been recorded, represented by elusive species which produce small amounts of venom. Due to advances in genomics and transcriptomics, the availability of toxin sequences from venomous mammals has been increasing. Using branch- and site-specific selection models, we present the rates of both episodic and pervasive selection acting upon venomous mammal toxins as a group for the first time. We identified seven toxin groups present within venomous mammals, representing Chiroptera, Eulipotyphla and Monotremata: KLK1, Plasminogen Activator, Desmallipins, PACAP, CRiSP, Kunitz Domain One and Kunitz Domain Two. All but one group (KLK1) was identified by our results to be evolving under both episodic and pervasive diversifying selection with four toxin groups having sites that were implicated in the fitness of the animal by TreeSAAP (Selection on Amino Acid Properties). Our results suggest that venomous mammal ecology, behaviour or genomic evolution are the main drivers of selection, although evolutionary age may still be a factor. Our conclusion from these results indicates that mammalian toxins are following the two-speed model of selection, evolving predominately under diversifying selection, fitting in with other younger venomous taxa like snakes and cone snails-with high amounts of accumulating mutations, leading to more novel adaptions in their toxins.


Assuntos
Quirópteros , Toxinas Biológicas , Animais , Toxinas Biológicas/genética , Toxinas Biológicas/toxicidade , Mamíferos/genética , Peçonhas/genética , Peçonhas/toxicidade , Serpentes , Perfilação da Expressão Gênica , Evolução Molecular
9.
Toxins (Basel) ; 14(12)2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36548743

RESUMO

The venoms of ants (Formicidae) are a promising source of novel bioactive molecules with potential for clinical and agricultural applications. However, despite the rich diversity of ant species, only a fraction of this vast resource has been thoroughly examined in bioprospecting programs. Previous studies focusing on the venom of Central European ants (subfamily Myrmicinae) identified a number of short linear decapeptides and nonapeptides resembling antimicrobial peptides (AMPs). Here, we describe the in silico approach and bioactivity profiling of 10 novel AMP-like peptides from the fellow Central European myrmicine ants Myrmica rubra and Myrmica ruginodis. Using the sequences of known ant venom peptides as queries, we screened the venom gland transcriptomes of both species. We found transcripts of nine novel decapeptides and one novel nonapeptide. The corresponding peptides were synthesized for bioactivity profiling in a broad panel of assays consisting of tests for cytotoxicity as well as antiviral, insecticidal, and antimicrobial activity. U-MYRTX-Mrug5a showed moderately potent antimicrobial effects against several bacteria, including clinically relevant pathogens such as Listeria monocytogenes and Staphylococcus epidermidis, but high concentrations showed negligible cytotoxicity. U-MYRTX-Mrug5a is, therefore, a probable lead for the development of novel peptide-based antibiotics.


Assuntos
Venenos de Formiga , Anti-Infecciosos , Formigas , Animais , Formigas/genética , Peptídeos/química , Transcriptoma , Peçonhas , Venenos de Formiga/toxicidade , Venenos de Formiga/química
10.
Epidemiol Serv Saude ; 31(3): e2022025, 2022.
Artigo em Português, Inglês | MEDLINE | ID: mdl-36351057

RESUMO

OBJECTIVE: to analyze the temporal trend of accidents involving venomous animals in Brazil from 2007 to 2019. METHODS: this was a cross-sectional study carried out with data from the Notifiable Health Conditions Information System (SINAN). Prais-Winsten linear regression was used for the temporal analysis. We calculated incidence rates according to sex and age group, relative risk and case fatality ratio. RESULTS: during the study period there were 2,102,657 cases of accidents involving venomous animals. With the exception of snakebite, the remaining accidents showed a rising temporal trend in most regions of the country. Scorpion stings, snake bites and spider bites were responsible for 86% of accidents, mainly affecting male people of working age. Accidents involving snakes (0.4%) and bees (0.3%) had the highest case fatality ratios. Children were the main victims of accidents involving bees, caterpillars and "others". CONCLUSION: accidents involving venomous animals showed a rising temporal trend for most conditions, as well as different epidemiological profiles.


Assuntos
Mordeduras de Serpentes , Peçonhas , Masculino , Animais , Abelhas , Brasil/epidemiologia , Estudos Transversais , Mordeduras de Serpentes/epidemiologia , Acidentes
11.
Rev Soc Bras Med Trop ; 55: e02162022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36351061

RESUMO

BACKGROUND: Freshwater stingrays are fish that have adapted to the rivers and lakes in South America. The expansion of the Potamotrygonidae family in the Paraná River began after the damming of the Sete Quedas Falls, reaching the mouth of the Paranapanema and Tietê rivers approximately 20 years ago via the locks of the hydroelectric power plants. They are not aggressive animals; however, they have one to four stingers on their tails covered by a venom-producing epithelium and can cause severe envenomation in fishermen and bathers if stepped on or manipulated. METHODS: We conducted a descriptive, retrospective, and prospective study by monitoring the fishing of the Potamotrygon genus in the lower Tietê River, mapping the location of the rays as a fishery product of professional fishermen and/or recording images of the fish caught. RESULTS: Sixteen stingrays of the Potamotrygon genus were mapped by monitoring fishermen's fish products in the extensive area between the municipalities of Pereira Barreto and Buritama, São Paulo state. CONCLUSIONS: The lower Tietê River is fully colonized by freshwater stingrays and this expansion likely continues upstream, reaching various sub-basins of the river. The advancement of these venomous fish in areas where they did not exist previously requires education programs and interaction with the community to avoid serious injuries in bathers and fishermen and the unreasonable extermination of the animals.


Assuntos
Rajidae , Animais , Brasil , Rios , Peçonhas , Estudos Prospectivos , Estudos Retrospectivos
12.
Toxins (Basel) ; 14(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36422973

RESUMO

Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors. Conus striatus, one of the largest piscivorous species, is widely distributed, from east African coasts to remote Polynesian Islands. In this study, we investigated potential intraspecific differences in venom composition between distinct geographical populations from Mayotte Island (Indian Ocean) and Australia (Pacific Ocean). Significant variations were noted among the most abundant components, namely the κA-conotoxins, which contain three disulfide bridges and complex glycosylations. The amino acid sequence of a novel κA-conotoxin SIVC, including its N-terminal acetylated variant, was deciphered using tandem mass spectrometry (MS/MS). In addition, the glycosylation pattern was found to be consisting of two HexNAc and four Hex for the Mayotte population, which diverge from the previously characterized two HexNAc and three Hex combinations for this species, collected elsewhere. Whereas the biological and ecological roles of these modifications remain to be investigated, population-specific glycosylation patterns provide, for the first time, a new level of intraspecific variations in cone snail venoms.


Assuntos
Conotoxinas , Caramujo Conus , Animais , Caramujo Conus/química , Conotoxinas/química , Peçonhas/metabolismo , Proteômica , Espectrometria de Massas em Tandem
13.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362117

RESUMO

The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed "pararamosis". To date, there is still no specific treatment for pararamosis. In this study, we used a whole human blood model to evaluate the involvement of the complement in the proinflammatory effects of P. semirufa hair extract, as well as the anti-inflammatory potential of complement inhibitors in this process. After treatment of blood samples with the P. semirufa hair extract, there was a significant increase in the generation of soluble terminal complement complex (sTCC) and anaphylatoxins (C3a, C4a, and C5a), as well as the production of the cytokines TNF-α and IL-17 and the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10. The inhibition of C3 with compstatin significantly decreased IL-17, IL-8, RANTES, and MCP-1 production. However, the use of the C5aR1 antagonist PMX205 promoted a reduction in the production of IL-8 and RANTES. Moreover, compstatin decreased CD11b, C5aR1, and TLR2 expression induced by P. semirufa hair extract in granulocytes and CD11b, TLR4, and TLR2 in monocytes. When we incubated vascular endothelial cells with extract-treated human plasma, there was an increase in IL-8 and MCP-1 production, and compstatin was able to decrease the production of these chemokines. C5aR1 antagonism also decreased the production of MCP-1 in endothelial cells. Thus, these results indicate that the extract of the Pararama bristles activates the complement system and that this action contributes to the production of cytokines and chemokines, modulation of the expression of surface markers in leukocytes, and activation of endothelial cells.


Assuntos
Mariposas , Animais , Humanos , Mariposas/metabolismo , Interleucina-17/efeitos adversos , Peçonhas , Interleucina-8 , Células Endoteliais/metabolismo , Floresta Úmida , Receptor 2 Toll-Like , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Proteínas do Sistema Complemento , Quimiocinas
14.
Wilderness Environ Med ; 33(4): 386-398, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36244888

RESUMO

INTRODUCTION: -Thrombotic microangiopathy (TMA), which is the triad of acute kidney injury (AKI), microangiopathic hemolytic anemia (MAHA), and thrombocytopenia, is a rare complication of snakebites, and in Sri Lanka, it is commonly seen with hump-nosed pit viper (HNPV) bites. METHODS: -We conducted a prospective observational study of patients with AKI caused by HNPV bites in Teaching Hospital, Ratnapura, Sri Lanka for 6 y, commencing in June 2015. Some patients with TMA underwent therapeutic plasma exchange (TPE) and some did not. These 2 groups were compared. Statistical analysis was carried out using Minitab 18.1. Data were presented as median (IQR). RESULTS: -There were 52 (8%) patients with TMA, of whom 21 (45%) were in the TPE group and 26 (55%) were in the non-TPE group. TPE improved time to platelet correction (4 d [IQR, 4-5 d] vs 7 d [IQR, 5-9 d]; P=0.009), time to MAHA correction (5 d [IQR, 3-4 d] vs 7 d [IQR, 6-9 d]; P=0.004), time to prothrombin time (PT)/international normalized ratio (INR) correction (1 d [IQR, 1-2 d] vs 3 d [IQR, 3-4 d]; P=0.003), and time to 20 min whole blood clotting test (WBCT20) correction (2 d [IQR, 1-2 d] vs 3 d [1QR 2-3 d]; P=0.020). Renal recovery was predicted by TPE (P=0.048) and highest creatinine level (P=0.001). There was no association between TPE and dialysis dependency at discharge (P=0.597), length of hospital stay (P=0.220), and the number of dialysis cycles prior to discharge (P=0.540). TPE did not improve the number of blood transfusions (5 packs [IQR, 3-8.5 packs] vs 4 packs [IQR, 0-9 packs]; P=0.290). CONCLUSIONS: -TPE is effective for TMA in the early correction of platelet counts, MAHA, PT/INR, and WBCT20 in HNPV bites.


Assuntos
Injúria Renal Aguda , Anemia Hemolítica , Crotalinae , Púrpura Trombocitopênica Trombótica , Mordeduras de Serpentes , Microangiopatias Trombóticas , Animais , Humanos , Troca Plasmática/efeitos adversos , Peçonhas/efeitos adversos , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , Microangiopatias Trombóticas/terapia , Microangiopatias Trombóticas/induzido quimicamente , Anemia Hemolítica/induzido quimicamente , Púrpura Trombocitopênica Trombótica/terapia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Sri Lanka
16.
Toxins (Basel) ; 14(10)2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36287926

RESUMO

Longitudinal metabolomics and lipidomics analyses were carried out on the blood plasma of mice injected intramuscularly with venoms of the viperid species Bothrops asper or Daboia russelii. Blood samples were collected 1, 3, 6, and 24 h after venom injection, and a control group of non-envenomed mice was included. Significant perturbations in metabolomics and lipidomics were observed at 1, 3, and 6 h, while values returned close to those of control mice by 24 h, hence reflecting a transient pattern of metabolic disturbance. Both venoms induced significant changes in amino acids, as well as in several purines and pyrimidines, and in some metabolites of the tricarboxylic acid cycle. KEGG analysis of metabolic pathways that showed those with the greatest change included aminoacyl tRNA synthesis and amino acid biosynthesis and metabolism pathways. With regard to lipid metabolism, there was an increase in triglycerides and some acyl carnitines and a concomitant drop in the levels of some phospholipids. In addition, envenomed mice had higher levels of cortisol, heme, and some oxidative stress markers. The overall pattern of metabolic changes in envenomed mice bears similarities with the patterns described in several traumatic injuries, thus underscoring a metabolic response/adaptation to the injurious action of the venoms.


Assuntos
Bothrops , Venenos de Crotalídeos , Víbora de Russell , Camundongos , Animais , Bothrops/metabolismo , Lipidômica , Hidrocortisona , Modelos Animais de Doenças , Víbora de Russell/metabolismo , Peçonhas/metabolismo , Aminoácidos/metabolismo , Purinas/metabolismo , Heme/metabolismo , Triglicerídeos/metabolismo , Pirimidinas/metabolismo , RNA de Transferência/metabolismo , Venenos de Crotalídeos/toxicidade , Venenos de Crotalídeos/metabolismo , Antivenenos/farmacologia
17.
G3 (Bethesda) ; 12(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226801

RESUMO

Many lizard species face extinction due to worldwide climate change. The Guatemalan Beaded Lizard, Heloderma charlesbogerti, is a member of the Family Helodermatidae that may be particularly imperiled; fewer than 600 mature individuals are believed to persist in the wild. In addition, H. charlesbogerti lizards are phenotypically remarkable. They are large in size, charismatically patterned, and possess a venomous bite. Here, we report the draft genome of the Guatemalan Beaded Lizard using DNA from a wild-caught individual. The assembled genome totals 2.31 Gb in length, similar in size to the genomes of related species. Single-copy orthologs were used to produce a novel molecular phylogeny, revealing that the Guatemalan Beaded Lizard falls into a clade with the Asian Glass Lizard (Anguidae) and in close association with the Komodo Dragon (Varanidae) and the Chinese Crocodile Lizard (Shinisauridae). In addition, we identified 31,411 protein-coding genes within the genome. Of the genes identified, we found 504 that evolved with a differential constraint on the branch leading to the Guatemalan Beaded Lizard. Lastly, we identified a decline in the effective population size of the Guatemalan Beaded Lizard approximately 400,000 years ago, followed by a stabilization before starting to dwindle again 60,000 years ago. The results presented here provide important information regarding a highly endangered, venomous reptile that can be used in future conservation, functional genetic, and phylogenetic analyses.


Assuntos
Lagartos , Humanos , Animais , Lagartos/genética , Filogenia , Densidade Demográfica , Peçonhas/genética , Genoma
18.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292948

RESUMO

The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of Conus obscurus (α-conotoxin OI) and identified the presence of α-conotoxin SI-like sequence previously found in the venom of Conus striatus. Five synthetic analogs of the native α-conotoxin OI were generated. These analogs incorporated single residue or double residue mutations. Three synthetic post-translational modifications (PTMs) were synthetically incorporated into these analogs: N-terminal truncation, proline hydroxylation, and tryptophan bromination. The native α-conotoxin OI demonstrated nanomolar potency in Poecilia reticulata and Homosapiens muscle-type nicotinic acetylcholine receptor (nAChR) isoforms. Moreover, the synthetic α-[P9K] conotoxin OI displayed enhanced potency in both bioassays, ranging from a 2.85 (LD50) to 18.4 (IC50) fold increase in comparative bioactivity. The successful incorporation of PTMs, with retention of both potency and nAChR isoform selectivity, ultimately pushes new boundaries of peptide bioengineering and the generation of novel α-conotoxin-like sequences.


Assuntos
Conotoxinas , Caramujo Conus , Receptores Nicotínicos , Animais , Caramujo Conus/química , Peçonhas , Triptofano/metabolismo , Conotoxinas/genética , Conotoxinas/química , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Peptídeos/metabolismo , Bioengenharia , Prolina/metabolismo
19.
Proc Biol Sci ; 289(1982): 20221132, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36300520

RESUMO

Traits for prey acquisition form the phenotypic interface of predator-prey interactions. In venomous predators, morphological variation in venom delivery apparatus like fangs and stingers may be optimized for dispatching prey. Here, we determine how a single dimension of venom injection systems evolves in response to variation in the size, climatic conditions and dietary ecology of viperid snakes. We measured fang length in more than 1900 museum specimens representing 199 viper species (55% of recognized species). We find both phylogenetic signal and within-clade variation in relative fang length across vipers suggesting both general taxonomic trends and potential adaptive divergence in fang length. We recover positive evolutionary allometry and little static allometry in fang length. Proportionally longer fangs have evolved in larger species, which may facilitate venom injection in more voluminous prey. Finally, we leverage climatic and diet data to assess the global correlates of fang length. We find that models of fang length evolution are improved through the inclusion of both temperature and diet, particularly the extent to which diets are mammal-heavy diets. These findings demonstrate how adaptive variation can emerge among components of complex prey capture systems.


Assuntos
Dente , Viperidae , Animais , Filogenia , Dente/anatomia & histologia , Viperidae/anatomia & histologia , Peçonhas , Dieta , Mamíferos
20.
J R Coll Physicians Edinb ; 52(3): 232-239, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36300884

RESUMO

BACKGROUND: Venom induced consumption coagulopathy (VICC) and its underlying mechanisms have not been fully elucidated in viperid envenomation (VE), especially among Indian patients. We evaluated for VICC in VE, assessed the performance of 20-min whole blood clotting test (20WBCT) for VICC detection and also studied predictors of VICC. METHODS: This hospital-based observational study enrolled 103 consecutive patients (age ⩾ 12 years) of snakebite admitted within 24 h of bite, with features of VE. They underwent 20WBCT, prothrombin time (PT)/international normalised ratio (INR), plasma fibrinogen and D-dimer testing during first 24 h after enrolment. Overt VICC (defined by overt bleeding), subclinical VICC (INR ⩾ 1.4 and/or fibrinogen < 2g/L, without overt bleeding), disseminated intravascular coagulation (DIC) (overt/non-overt, defined based on International Society on Thrombosis and Haemostasis (ISTH) DIC score) and primary defibrination (PDF) were evaluated among patients. RESULTS: VICC overall was noted in 77 (≈75%) and overt VICC in 52 (≈50%). DIC (overt/non-overt) was noted in 59 (≈77%) and PDF in 2 (2.6%) patients with VICC. Sensitivity, specificity, positive predictive value and negative predictive value of 20WBCT for VICC detection were 98.7% (95%CI: 92.9-99.9%), 65.4% (95%CI: 44.3-82.8%), 89.4% (95%CI: 83.3-93.5%) and 94.4% (95%CI: 70.4-99.2%) respectively. Severe cellulitis in bitten limb predicted reduced VICC risk. DISCUSSION: Majority (75%) of patients with VE had VICC and 68% with VICC had overt bleeding. DIC (overt/non-overt) was the predominant contributor to VICC. Though 20WBCT is a good screening test for VICC, false positive results should be kept in mind before deciding on snake antivenom treatment.


Assuntos
Coagulação Intravascular Disseminada , Humanos , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , Peçonhas , Fibrinogênio , Hemorragia , Coagulação Sanguínea , Dacarbazina
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