A bacteriolytic agent that detects and kills Bacillus anthracis

A bacteriolytic agent that detects and kills Bacillus anthracis
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DOI:
10.1038/nature01026
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发表时间:
2002-08-22
期刊:
影响因子:
64.8
通讯作者:
Fischetti, VA
Fischetti, VA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Schuch, R;Nelson, D;Fischetti, VA

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炭疽芽孢杆菌休眠和持久的孢子形式是一种理想的大规模杀伤性生物武器(1,2)。一旦被吸入,孢子由肺泡巨噬细胞运送到肺周围的淋巴结,在那里发芽;随后的植物扩张导致大量细菌和毒素进入血液,未经治疗的受害者死亡率高达99%。天然的和基因工程的耐抗生素杆菌增加了孢子被用作武器的威胁,并在故意释放后提高了改进治疗和孢子检测方法的必要性。我们利用噬菌体酶lysins固有的结合特异性和裂解作用来快速检测和杀灭炭疽芽孢杆菌。本研究表明,从炭疽芽孢杆菌γ噬菌体中分离出的PlyG溶酶在体外和体内特异性地杀死炭疽芽孢杆菌分离株和其他芽孢杆菌“簇”成员。营养细胞和发芽孢子都易受影响。PlyG的裂解特异性也被用作快速鉴定炭疽芽孢杆菌的方法之一。我们认为,PlyG是一种治疗和检测炭疽杆菌的工具。
The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction(1,2). Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic- resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploited the inherent binding specificity and lytic action of bacteriophage enzymes called lysins for the rapid detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated from the gamma phage of B. anthracis, specifically kills B. anthracis isolates and other members of the B. anthracis 'cluster' of bacilli in vitro and in vivo. Both vegetative cells and germinating spores are susceptible. The lytic specificity of PlyG was also exploited as part of a rapid method for the identification of B. anthracis. We conclude that PlyG is a tool for the treatment and detection of B. anthracis.