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Substances of Milky Juice of Genus Lactarius Fungi: Chemical and Toxicological Characteristics 乳菌属乳汁的化学及毒理学特征
Pub Date : 2023-02-01 DOI: 10.2174/2666121702666220822125947
Volodymyr O. Antonyuk, LydiaV. Panchak, Mariana V. Tsivinska, Rostyslav S. Stoika
Background: Fungi of the genus Lactarius Pers. before the maturation of spores are not damaged by microorganisms, insects, mollusks, and animals. Such resistance correlates with the period when the basidiomes of these fungi are filled with milky juice, which contains substances of various chemical nature that provide their protection. Objective: The aim of our work is to present the results of our recent and previously published studies on the identification and toxicological characteristics of substances available in the milky juice of fungi of the genus Lactarius Pers and used for protection against predator and parasite organisms. The possibility of using these substances to suppress tumor cells is also discussed. Methods: The biological effect of the juice of L. pergamenus, L. quietus, and L. volemus, as well as methylene chloride, extracts obtained from fresh, frozen and dried basidiomes of L. pergamenus was studied. Purification of individual fractions of hexane extract from the basidiomes was performed by chromatography on a silica gel column and their analysis by done by thin layer chromatography and gas chromatography mass spectrometry. Results: The sesquiterpene aldehydes were shown to be the main component of the chemical protection system of Lactarius. These agents are present in the milky juice of the Lactarius fungi, and they are easily oxidized by oxygen in the air. The milky juice of these mushrooms is also rich in higher fatty acids and phthalates. Phthalates possess an insecticidal effect, while higher fatty acids are capable of forming adducts with sesquiterpenes that provide emulsion stability. Water-soluble substances, in particular, the polyphenol oxidase enzyme, whose activity correlates with the content of milky juice in basidiomes, also play a protective role. Conclusion: Milky juice of mushrooms of Lactarius Pers. genus is a stable balanced emulsion containing a large number of substances. One part is responsible for the toxic effects on other organisms, while the other part determines the chemical stability of the emulsion. Altogether, they create an effective system of protection of fungi of the Lactarius genus against microorganisms, insects, mollusks, and animals.
背景:乳酸菌属真菌。孢子成熟前不受微生物、昆虫、软体动物和动物的破坏。这种抗性与这些真菌的担子子充满乳白色汁液的时期有关,乳白色汁液含有各种化学性质的物质,为它们提供保护。目的:介绍我们最近和以前发表的关于乳汁中可用于防止捕食者和寄生虫生物的物质的鉴定和毒理学特性的研究结果。还讨论了利用这些物质抑制肿瘤细胞的可能性。方法:采用鲜、冻、干三种不同原料提取的二氯甲烷,对羊草、小羊草、大羊草汁液的生物效应进行研究。采用硅胶柱层析法对担子子中己烷提取物进行分离纯化,并采用薄层色谱法和气相色谱质谱法对其进行分析。结果:倍半萜醛是乳酸菌化学防护体系的主要成分。这些物质存在于乳真菌的乳白色汁液中,它们很容易被空气中的氧气氧化。这些蘑菇的乳白色汁液也富含较高的脂肪酸和邻苯二甲酸盐。邻苯二甲酸酯具有杀虫作用,而较高的脂肪酸能够与倍半萜形成加合物,提供乳液稳定性。水溶性物质,特别是多酚氧化酶,其活性与担子体内乳汁的含量有关,也起着保护作用。结论:乳酸菌菇乳汁;Genus是一种含有大量物质的稳定平衡乳液。其中一部分负责对其他生物体的毒性作用,而另一部分则决定乳剂的化学稳定性。总之,它们创造了一个有效的系统,保护乳酸菌属的真菌免受微生物、昆虫、软体动物和动物的侵害。
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引用次数: 0
In-vitro and in-vivo neutralization activity of methanol extract of Adansonia digitata fruit pulp against Naja nigricollis venom 水杨花果肉甲醇提取物对黑颈病毒体外和体内中和活性的研究
Pub Date : 2022-12-13 DOI: 10.2174/2666121703666221213122738
D. Sani, John Oluwamayokun Elijah, M. Mamman, P. Yusuf, K. Jolayemi, Mary Oluwatomisin Elijah, M. Ameh, D. Otie
Adansonia digitata has been used as a traditional medicine to treat various diseases including snakebite envenomation.In this study, the protective and ameliorative potentials of crude methanol extract of Adansonia digitata fruit pulp against crude venom of Naja nigricollis in-vitro and in-vivo were investigated.The dose-dependent inhibitory studies, pharmacological, histopathological and in vivo studies were conducted using standard methods.The mean lethal dose of the crude methanolic extract of Adansonia digitata fruit pulp in Wistar rats was >5,000 mg/kg, while Naja nigricollis venom was 0.89 mg/kg. The anti-lethality effective concentration of the fruit pulp on Naja nigricollis venom was 92.52 mg/ml. Treatment significantly (p < 0.05) inhibited the activities of Naja nigricollis phospholipase A2 and dose-dependently reduced Naja nigricollis venom-induced paw oedema at 1-4 hours post-envenomation. In-vivo, treatment with 250 and 500 mg/kg of Adansonia digitata fruit pulp was protective against the clinical signs and mortality. Serum acetylcholinesterase activities were maintained in the group treated with normal saline and the ameliorative groups but decreased significantly (p < 0.05) in other groups. Brain acetylcholinesterase was high in all the groups by day 1 but was reduced with increasing dose by day 2 in the ameliorative groups only. Adansonia digitata fruit pulp also preserved the histoarchitecture of the brain, heart, liver and spleen from venom-induced pathologies.Crude methanolic extract of Adansonia digitata fruit pulp possesses good protective and ameliorative neutralization effects on Naja nigricollis venom and could be promising in the management of snakebite envenomation.
adansononia digitata已被用作传统药物治疗各种疾病,包括蛇咬伤中毒。在体外和体内研究了荆芥果肉粗甲醇提取物对黑颈蛇粗毒液的保护和改善作用。使用标准方法进行剂量依赖性抑制研究、药理学、组织病理学和体内研究。麻桃果肉粗甲醇提取物对Wistar大鼠的平均致死剂量> 5000 mg/kg,黑毛蛇毒液对Wistar大鼠的平均致死剂量为0.89 mg/kg。果肉对黑毛蛇毒液的抗毒有效浓度为92.52 mg/ml。处理显著(p < 0.05)抑制了黑僵鼠磷脂酶A2的活性,并在毒后1 ~ 4小时剂量依赖性地减少了黑僵鼠毒液引起的足跖水肿。在体内,250和500 mg/kg的adansononia digitata果肉对临床症状和死亡率有保护作用。生理盐水处理组和改良组血清乙酰胆碱酯酶活性维持正常,其余各组血清乙酰胆碱酯酶活性显著降低(p < 0.05)。脑乙酰胆碱酯酶在第1天各组均较高,仅改良组在第2天随剂量增加而降低。adansononia digitata果肉还保留了毒液引起的脑组织、心脏、肝脏和脾脏的组织结构。洋桃果肉粗甲醇提取物对黑毛小蛇蛇毒具有良好的保护和改善中和作用,在蛇咬伤中毒治疗中具有广阔的应用前景。
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引用次数: 0
Evaluation of the Toxic effects of Bothrops jararacussu Snake Venom on Zebrafish (Danio rerio) embryos and larvae 贾拉沙鼠蛇毒对斑马鱼胚胎和幼鱼的毒性作用评价
Pub Date : 2022-09-29 DOI: 10.2174/2666121702666220929153903
D. P. Marchi-Salvador, Layssa Gualberto da Silva, Pedro Gabriel Nascimento dos Santos, Juliana Alves Costa Ribeiro Souza, R. X. Martins, Pierri Emanoel de Abreu Oliveira, D. Farias
Approximately 90% of reported and identified cases of snakebite in Brazil are caused by species belonging to the Bothrops genus. These snakes have clinical relevance due to their venom composition, which contains substances capable of triggering local and systemic effects culminating in the development of morbidities and mortality in the affected individual.This study aims to evaluate the toxic and toxinological effects of Bothrops jararacussu snake venom on zebrafish embryos and larvae. B. jararacussu venom’s stability, under the conditions used in the toxicity experiments in zebrafish embryos and larvae was evaluated on citrated human plasma by measuring the prothrombin and activated partial thromboplastin times.Mortality, morphological alterations, spontaneous tail movements, heartbeat, toxicity parameters and activity of enzymes biomarkers of toxicity were evaluated in zebrafish embryos and/or larvae after exposure to the venom. Acute toxicity was assessed by semi-static exposure of zebrafish embryos to venom for 96 hours.The results indicated that the venom causes toxicity in zebrafish embryos and larvae, inducing embryonic mortality, alteration in the number of spontaneous tail movements and activity of biomarker enzymes. The results suggest that the toxic effects caused by the venom in the early stages of zebrafish development are mediated, in part, by neurotoxic action, and induction of oxidative and metabolic stress caused by low molecular weight components and proteins present in this venom.Toxinological evaluations using the zebrafish as a model are scarce; however, this study presented promising results that encourage the development of future research in toxinology using this animal as a model organism.
在巴西报告和确定的蛇咬伤病例中,约90%是由Bothrops属的物种引起的。这些蛇具有临床意义,因为它们的毒液成分含有能够引发局部和全身影响的物质,最终导致受影响个体的发病率和死亡率的发展。摘要本研究旨在评价jararacussu Bothrops蛇毒对斑马鱼胚胎和幼鱼的毒性和毒理学作用。通过测定血凝酶原和活化的部分凝血活酶时间,评价了黄毒在斑马鱼胚胎和幼虫毒性实验条件下的稳定性。在斑马鱼胚胎和/或幼虫接触毒液后,对其死亡率、形态改变、自发尾巴运动、心跳、毒性参数和毒性生物标志物酶的活性进行了评估。急性毒性是通过将斑马鱼胚胎半静态暴露于毒液中96小时来评估的。结果表明,该毒液可引起斑马鱼胚胎和幼虫的毒性,导致胚胎死亡,改变自发尾运动的数量和生物标记酶的活性。结果表明,在斑马鱼发育的早期阶段,该毒液引起的毒性作用部分是通过神经毒性作用以及由该毒液中存在的低分子量成分和蛋白质引起的氧化和代谢应激介导的。使用斑马鱼作为模型的毒性评估很少;然而,这项研究提出了有希望的结果,鼓励了未来以这种动物为模式生物的毒理学研究的发展。
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引用次数: 0
Meet the Editorial Board Member
Pub Date : 2022-08-01 DOI: 10.2174/266612170202221122163207
D. P. Marchi-Salvador
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引用次数: 0
Snake Envenomation And Innate Immune System: An Overview 蛇毒和先天免疫系统:综述
Pub Date : 2022-05-23 DOI: 10.2174/2666121702666220523140901
M. Reis, Anna Caroline Vendrame Cazeloto, Julia Breda Roque, Juliana Cogo Ferreira, Marianna Minaré Vigo, K. F. Zoccal
Snake envenomations are one of the most common venomous accidents caused by animals in the world. The symptoms induced after bite vary accordingly to the species. Most of the snake venoms elicit direct or indirect activation of the innate immune responses that ranges from local to systemic effects and contributes to the clinical manifestations after envenoming. The venom interacts with the immune system by inducing the release of damage-associated molecular patterns, which contributes to create a proinflamatory status, release of cytokines and lipid mediators, and has properties to modulate other components of the innate immune system like the complement system. In this review, we highlitht some studies that point out over the years the mechanisms by which snake venoms interact with the innate immune system, as well as the pharmacological potential of this class of compounds with great applicability to the medical field.
蛇中毒是世界上由动物引起的最常见的中毒事故之一。咬伤后引起的症状因种类而异。大多数蛇毒引起直接或间接的先天免疫反应,其作用范围从局部到全身,并有助于中毒后的临床表现。毒液通过诱导释放与损伤相关的分子模式来与免疫系统相互作用,这有助于创造促炎状态,释放细胞因子和脂质介质,并具有调节先天免疫系统(如补体系统)的其他组成部分的特性。本文综述了近年来有关蛇毒与先天免疫系统相互作用机制的一些研究,以及该类化合物在医学领域的应用潜力。
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引用次数: 0
Toxins from venomous arthropods in Brazil: patents and potential biotechnological applications 巴西有毒节肢动物的毒素:专利和潜在的生物技术应用
Pub Date : 2022-05-23 DOI: 10.2174/2666121702666220523143235
Pedro Henrique Cardoso de Castro, A. L. Paiva, Barbara B R Oliveira-Mendes, C. Guerra-Duarte, Alessandra Matavel
The diversity of components in arthropod venoms constitute a rich source of bioactive molecules. Brazil is the most biodiverse country of the world, comprising 15 to 20% of the total catalogued species, with approximately 103,870 animal species including arthropods. Although many articles mention the biotechnological potential of these venoms and toxins, only few studies compile the patented uses of these molecules.This review describes the knowledge about the molecular mechanism of venoms and toxins with biotechnological potential, and list the patents deposited up to 2021 related to the main medical relevant arthropods in Brazil including the orders Araneae (spider genus Phoneutria, Loxosceles, Latrodectus), Scorpiones (scorpion genus Tityus), Lepidoptera (caterpillar genus Lonomia), and Hymenoptera.The international patent search engine “Espacenet” and the “Brazilian patent office” were used to search the patents described in this article.Up to date, 34 patents have been filled involving these Brazilian arthropods' venoms or toxins. Most of them (20) claimed biotechnological inventions with spider toxins, mainly from the genus Phoneutria. Only seven inventions involved venom or toxins from scorpions, one from bee, three from wasps, and three from caterpillars.Brazil is one of the main references in venoms and toxins’ studies; however, the limited number of deposited patents related to this area by Brazilian researchers do not reflect their pioneer position in this field. On the other hand, patents were well described and made with purified toxins, rather than with the whole venom. Nevertheless, the vast publication record of venom and toxin characterization that leads to a better understanding of their molecular mechanisms paves the way for turning these promising molecules into possible products.
节肢动物毒液成分的多样性构成了生物活性分子的丰富来源。巴西是世界上生物多样性最丰富的国家,拥有包括节肢动物在内的约103,870种动物,占已编目物种总数的15%至20%。尽管许多文章提到了这些毒液和毒素的生物技术潜力,但只有少数研究汇编了这些分子的专利用途。本文综述了具有生物技术潜力的毒液和毒素分子机制方面的知识,并列举了巴西截至2021年的主要医学相关节肢动物专利,包括蜘蛛目(蜘蛛属Phoneutria、Loxosceles、Latrodectus)、蝎目(蝎属Tityus)、鳞翅目(毛虫属Lonomia)和膜翅目。使用国际专利搜索引擎“Espacenet”和“巴西专利局”对本文中描述的专利进行了搜索。到目前为止,已经有34项专利涉及这些巴西节肢动物的毒液或毒素。他们中的大多数(20)声称使用蜘蛛毒素的生物技术发明,主要来自声索属。只有7项发明涉及蝎子的毒液或毒素,1项来自蜜蜂,3项来自黄蜂,3项来自毛毛虫。巴西是毒液和毒素研究的主要参考文献之一;然而,巴西研究人员提交的与这一领域相关的专利数量有限,并不能反映他们在这一领域的先锋地位。另一方面,专利被很好地描述和纯化毒素,而不是整个毒液。尽管如此,大量关于毒液和毒素特性的出版记录,使人们更好地了解它们的分子机制,为将这些有希望的分子转化为可能的产品铺平了道路。
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引用次数: 1
Current ion channel-targeted drugs and potential of venom-derived peptides as a therapeutic new modality 目前离子通道靶向药物和毒液衍生肽作为一种治疗新模式的潜力
Pub Date : 2022-04-29 DOI: 10.2174/2666121702666220429095250
Toshiaki Okada, H. Taira, Tadashi Kimura
Ion channel function is an essential mechanism for maintaining life and is involved in a variety of physiological activities. However, various factors such as heredity, aging, wounding, and diseases can cause abnormalities in ion channel function and expression. Such channel abnormalities can interfere with the healthy activities of the organism and threaten the maintenance of life. There are many types of ion channels, and their roles are diverse. In recent years, it is becoming clear that ion channels are intrinsically involved in a variety of diseases beyond what has been previously thought. Therefore, it is highly desirable to develop more drugs by increasing the variety of channels for drug discovery and the variety of diseases to be treated. In this review, we will introduce the ion channels that are currently targets for drug discovery and the mechanisms by which these channels are involved in diseases, focusing on information compiled on the Internet. Currently, the target ion channels for drug development and the diseases to be treated are becoming more diverse. The drugs under development are not only small molecules, which account for most of the ion channel drugs developed to date, but also different types of drugs, such as antibodies, peptides, and oligonucleotides. Many of existing ion channel drugs have side effect problems that may be due to their low specificity. Diversification of drugs may facilitate the resolution of these problems, and venom-derived peptide drugs are a promising class of future agents that can contribute to this end. In the last part of this review, the status of drug development of venom-derived peptides will also be discussed.
离子通道功能是维持生命的重要机制,参与多种生理活动。然而,遗传、衰老、损伤和疾病等多种因素可导致离子通道功能和表达异常。这种通道异常会干扰机体的健康活动,威胁生命的维持。离子通道的种类很多,作用也多种多样。近年来,人们越来越清楚地认识到,离子通道在本质上与多种疾病有关,超出了以前的认识。因此,通过增加药物发现渠道的多样性和治疗疾病的多样性来开发更多的药物是非常可取的。在这篇综述中,我们将介绍目前药物发现的靶点离子通道以及这些通道参与疾病的机制,重点介绍互联网上收集的信息。目前,药物开发的靶离子通道和治疗的疾病越来越多样化。正在开发的药物不仅是小分子药物,而且是不同类型的药物,如抗体、多肽和寡核苷酸,占迄今为止开发的离子通道药物的大部分。许多现有的离子通道药物存在副作用问题,这可能是由于它们的低特异性。药物的多样化可能有助于解决这些问题,而毒液衍生的肽药物是一种有前途的未来药物,可以为这一目标做出贡献。在本文的最后一部分,还将讨论毒液衍生肽的药物开发现状。
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引用次数: 0
Development and Validation of an ELISA to Evaluate Neutralizing Equine Anti Shiga Toxin Antibodies in Preclinical Studies ELISA法评价马抗志贺毒素抗体临床前研究的建立与验证
Pub Date : 2022-04-27 DOI: 10.2174/2666121702666220427081107
G. Santiago, Hiriart Yanina, L. Muñoz, F. Rey, G. Hein, Santiago Sanguineti, Vanesa Zylverman, H. Ortega, B. Marelli
Hemolytic uremic syndrome associated to Shiga-toxin produced by Escherichia coli is a serious worldwide foodborne disease. Nowadays, no treatment is available, only supportive care can be provided, and 50 % of the patients require a period of dialysis. Recently, a therapy based on Neutralizing Equine Anti Shiga Toxin (NEAST) antibodies has been developed. NEAST is composed of F(ab’)2 fragments from equine immunoglobulins.The purpose of this study was to develop an ELISA to measure serum concentrations of NEAST in mice and rabbits and to validate it according to international recommendations. The validated method was further used to analyze the NEAST PK during preclinical studies.A sandwich ELISA was developed, the performance of the calibration curve was assessed and it was validated based on the parameters as accuracy, precision, specificity, selectivity, stability of the analyte and dilutional linearity.This immunoassay was specific, sensitive, accurate and precise in a dynamic range from 7.81 to 500 ng/mL and from 15.63 to 500 ng/mL for mice and rabbits, respectively. This method was successfully applied to PK studies of NEAST after intravenous administration.The results obtained are the expected for a robust ELISA used for macromolecule analysis. Since NEAST is an equine F(ab′)2, this inmunoassay would serve for the evaluation of the PK profile of any biological product based on molecules with similar characteristics. This immunoassay may be useful for current and in future preclinical trials conducted for registration purposes.
由大肠杆菌产生的志贺毒素引起的溶血性尿毒症是一种严重的世界性食源性疾病。如今,没有治疗方法,只能提供支持性护理,50% %的患者需要一段时间的透析。最近,一种基于中和马抗志贺毒素(NEAST)抗体的治疗方法被开发出来。NEAST由马免疫球蛋白的F(ab’)2片段组成。本研究的目的是建立一种ELISA方法来测量小鼠和家兔血清中NEAST的浓度,并根据国际建议对其进行验证。在临床前研究中,进一步使用验证的方法分析NEAST PK。建立夹心酶联免疫吸附测定法(sandwich ELISA),根据准确度、精密度、特异性、选择性、分析物稳定性和稀释线性等参数,对标定曲线的性能进行评价。小鼠和家兔在7.81 ~ 500 ng/mL和15.63 ~ 500 ng/mL的动态范围内具有特异性、敏感性、准确性和精密度。该方法成功地应用于NEAST静脉给药后的PK研究。所获得的结果是预期的一个强大的ELISA用于大分子分析。由于NEAST是马的F(ab ')2,因此该免疫分析将用于基于具有相似特征的分子的任何生物制品的PK谱的评估。这种免疫分析可能对当前和未来为注册目的进行的临床前试验有用。
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引用次数: 0
Meet the Editorial Board Member 认识编辑委员会成员
Pub Date : 2022-04-01 DOI: 10.2174/266612170201220704141554
S. Dutertre
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引用次数: 0
Detection of Enterotoxin Genes in Bacillus species Isolated from Cassava Processing Environment in Nigeria. 尼日利亚木薯加工环境芽孢杆菌中肠毒素基因的检测
Pub Date : 2022-01-12 DOI: 10.2174/2666121702666220112101938
N. Torimiro, O. B. Daramola, Richard K OMOLE, Ifeyimika Z. Adesina
The health challenges associated with cassava products as a common staple food for approximately 70% of Africans and part of Asia pose a looming danger due to Bacillus enterotoxins’ presence in the processing environment.This study investigated the presence of enterotoxigenic genes namely, Bacillus cereus enterotoxin T (bceT), hemolysin bl (hblC, hblD) and non-haemolytic enterotoxin (nheA, nheB and nheC) from Bacillus species isolated from soil of cassava processing environment.Soil samples from 20 cassava processing sites in Ile-Ife and Modakeke, Nigeria were collected and cultured on Nutrient agar at 37 ºC for 24 hours. Colonies phenotypically identified as Bacillus were identified using Bacillus-specific 16S rRNA-targeted PCR technique. Screened Bacillus spp were assessed for the presence of enterotoxigenic genes using PCR with previously reported primers.A total of 100 Bacillus isolates were selected from this study with Bacillus macerans (33 %) showing the highest frequency of occurrence among the identified species, however, 74 isolates were molecularly confirmed as Bacillus. Amongst the 74 molecularly confirmed Bacillus isolates, 28 (37.84%), 35 (47.30 %) and 37 (50 %) has nhe, hbl and bceT genes respectively. Investigation showed that 42 (56.76 %) of the Bacillus species encoded at least one of the screened enterotoxin genes.The presence of these 3 sets of enterotoxin genes in Bacillus isolated from cassava processing sites calls for immediate attention as they could be pivotal in the release of toxins in cassava products, cause lethal effects via consumption. This study demonstrates the possibility of foodborne disease outbreaks in Bacillus toxin-laden cassava products processed under unhygienic conditions.
木薯产品是大约70%的非洲人和部分亚洲人的常见主食,加工环境中存在肠芽孢杆菌毒素,因此与木薯产品相关的健康挑战构成了迫在眉睫的危险。本研究研究了从木薯加工环境土壤中分离的芽孢杆菌中存在的产肠毒素基因,即蜡样芽孢杆菌肠毒素T (bceT)、溶血素bl (hblC、hblD)和非溶血性肠毒素(nheA、nheB和nheC)。从尼日利亚Ile-Ife和Modakeke的20个木薯加工地点收集土壤样本,并在37ºC的营养琼脂上培养24小时。采用Bacillus-specific 16S rRNA-targeted PCR技术对表型为芽孢杆菌的菌落进行鉴定。筛选后的芽孢杆菌用PCR方法和先前报道的引物检测产肠毒素基因的存在。本研究共分离了100株芽孢杆菌,其中以芽孢杆菌(33%)出现频率最高,但经分子鉴定为芽孢杆菌的有74株。经分子鉴定的74株芽孢杆菌中,nhe、hbl和bceT基因分别为28株(37.84%)、35株(47.30%)和37株(50%)。调查结果显示,42个芽孢杆菌(56.76%)至少编码了筛选到的一种肠毒素基因。从木薯加工现场分离的芽孢杆菌中存在这3组肠毒素基因,需要立即予以关注,因为它们可能是木薯产品中毒素释放的关键,通过食用造成致命影响。本研究表明,在不卫生的条件下加工的含有芽孢杆菌毒素的木薯产品可能发生食源性疾病暴发。
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引用次数: 1
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Venoms and Toxins
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