[转移贴]Nature：细菌免疫系统的秘密被揭开

cao1976

原贴由wwwkkk83发表于 2010-11-9 08:25

加拿大拉瓦尔大学和丹麦丹尼斯克公司的一组研究人员揭开了细菌免疫系统的秘密，这一发现有可能解决某些细菌对抗生素产生抗药性的难题。该研究发表于11月4日的《自然》杂志上。

由拉瓦尔大学生物化学、微生物学和生物信息学系西尔·莫埃努教授领导的研究小组发现，选择特定的外源DNA（脱氧核糖核酸）片段并将其嵌入到细菌基因组的特定区域，这些片段便可作为一种免疫因子，抵抗DNA裂解入侵。这种技术又被称为CRISPR/Cas技术。

研究人员利用质粒——一种可与细菌进行交换的DNA分子证明了这一机制。实验中，研究人员将载有抗生素抗性基因的质粒注入嗜热链球菌中。其中一些细菌将含有抗性基因的DNA片段整合到了其基因组中。随后的实验发现，这些细菌拥有了不再接受质粒嵌入的特性。莫埃努认为，这表明这些细菌获得了对抗性基因的免疫能力。这种现象也可以解释，为什么一些细菌能够发展出耐药性，而其他的细菌不具有耐药性。

CRISPR/Cas免疫机制还可以防止噬菌体污染。莫埃努认为，这一发现将对食品业、抗生素业及生物技术产业十分有益，因为噬菌体污染将大幅度增加这些行业的经济成本。

英文摘要：Nature doi:10.1038/nature09523

The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA
Josiane E. Garneau,Marie-ève Dupuis,Manuela Villion,Dennis A. Romero,Rodolphe Barrangou,Patrick Boyaval,Christophe Fremaux,Philippe Horvath,Alfonso H. Magadán& Sylvain

Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.