首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >From the Cover: Thuricin CD a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile
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From the Cover: Thuricin CD a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile

机译:从封面:Thuricin CD一种经翻译后修饰的细菌素对艰难梭菌具有窄谱活性

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摘要

The last decade has seen numerous outbreaks of Clostridium difficile-associated disease (CDAD), which presented significant challenges for healthcare facilities worldwide. We have identified and purified thuricin CD, a two-component antimicrobial that shows activity against C. difficile in the nanomolar range. Thuricin CD is produced by Bacillus thuringiensis DPC 6431, a bacterial strain isolated from a human fecal sample, and it consists of two distinct peptides, Trn-α and Trn-β, that act synergistically to kill a wide range of clinical C. difficile isolates, including ribotypes commonly associated with CDAD (e.g., ribotype 027). However, this bacteriocin thuricin CD has little impact on most other genera, including many gastrointestinal commensals. Complete amino acid sequencing using infusion tandem mass spectrometry indicated that each peptide is posttranslationally modified at its respective 21st, 25th, and 28th residues. Solution NMR studies on [13C,15N] Trn-α and [13C,15N]Trn-β were used to characterize these modifications. Analysis of multidimensional NOESY data shows that specific cysteines are linked to the α-carbons of the modified residues, forming three sulfur to α-carbon bridges. Complete sequencing of the thuricin CD gene cluster revealed genes capable of encoding two S′-adenosylmethionine proteins that are characteristically associated with unusual posttranslational modifications. Thuricin CD is a two-component antimicrobial peptide system with sulfur to α-carbon linkages, and it may have potential as a targeted therapy in the treatment of CDAD while also reducing collateral impact on the commensal flora.
机译:在过去十年中,艰难梭菌相关疾病(CDAD)爆发了无数次,这给全球医疗机构带来了严峻挑战。我们已经鉴定并纯化了苏里霉素CD,这是一种两组分抗菌剂,在纳摩尔范围内显示出对艰难梭菌的活性。苏云霉素CD由苏云金芽孢杆菌DPC 6431(一种从人粪便样品中分离出的细菌菌株)生产,它由两种截然不同的肽Trn-α和Trn-β组成,它们具有协同作用,可杀死多种临床艰难梭菌分离物。包括通常与CDAD相关的核糖型(例如,核糖型027)。但是,这种细菌素-苏氨酸CD对大多数其他属几乎没有影响,包括许多胃肠道疾病。使用注入串联质谱的完整氨基酸测序结果表明,每个肽段分别在其第21、25和28位残基进行了翻译后修饰。 [ 13 C, 15 N]Trn-α和[ 13 C, 15 N]的溶液NMR研究Trn-β用于表征这些修饰。多维NOESY数据的分析表明,特定的半胱氨酸与修饰残基的α-碳相连,形成了3个硫与α-碳的桥。苏里霉素CD基因簇的完整测序揭示了能够编码两个S'-腺苷甲硫氨酸蛋白的基因,这些蛋白通常与异常的翻译后修饰相关。苏里霉素CD是具有硫与α-碳键的两组分抗菌肽系统,在治疗CDAD的同时可能具有靶向治疗的潜力,同时还减少了对共生菌群的附带影响。

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