Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile
Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile
复制标题
DOI：
10.1128/jb.01272-12
复制
发表时间：
2012-11-01
影响因子：
3.2
通讯作者：
Scholl, Dean
中科院分区：
文献类型：
--
作者：
Gebhart, Dana;Williams, Steven R.;Scholl, Dean
在发达国家，艰难梭菌是导致医院感染的主要原因之一，治疗选择有限。部分菌株C.艰难梭菌在诱导SOS应答时产生噬菌体尾样颗粒。这些颗粒对其他C.艰难梭菌菌株的R型绿脓菌素，因此可以被分类为细菌素，类似于铜绿假单胞菌的R型绿脓菌素。这些R型细菌素颗粒是从不同的菌株中纯化出来的，每一种都具有不同的C。难杀谱，没有一种细菌素能杀死所有的C.检测的艰难分离株。我们已经确定了这些“艰难梭菌素”的遗传位点（开放阅读框1359至1376），并发现它们在物种中是常见的。克隆了大于20 kb的整个艰难梭菌素基因座，并在枯草芽孢杆菌中表达，这导致产生杀菌颗粒。这些颗粒的有趣特征之一是类似于200 kDa的非常大的结构蛋白，即基因1374的产物。这种大蛋白决定了颗粒的杀伤谱，很可能是受体结合蛋白。艰难梭菌素可以提供替代的杀菌剂，以预防或治疗感染，并使无症状携带者去定居。
Clostridium difficile causes one of the leading nosocomial infections in developed countries, and therapeutic choices are limited. Some strains of C. difficile produce phage tail-like particles upon induction of the SOS response. These particles have bactericidal activity against other C. difficile strains and can therefore be classified as bacteriocins, similar to the R-type pyocins of Pseudomonas aeruginosa. These R-type bacteriocin particles, which have been purified from different strains, each have a different C. difficile-killing spectrum, with no one bacteriocin killing all C. difficile isolates tested. We have identified the genetic locus of these "diffocins" (open reading frames 1359 to 1376) and have found them to be common among the species. The entire diffocin genetic locus of more than 20 kb was cloned and expressed in Bacillus subtilis, and this resulted in production of bactericidal particles. One of the interesting features of these particles is a very large structural protein of similar to 200 kDa, the product of gene 1374. This large protein determines the killing spectrum of the particles and is likely the receptor-binding protein. Diffocins may provide an alternate bactericidal agent to prevent or treat infections and to decolonize individuals who are asymptomatic carriers.