CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA.

CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA.
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DOI:
10.1126/science.1165771
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发表时间:
2008-12-19
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Sontheimer EJ
Sontheimer EJ
中科院分区:
其他
文献类型:
--
作者:
Marraffini LA;Sontheimer EJ

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细菌和古细菌中的水平基因转移(HGT)通过噬菌体转导、转化或接合发生,后者对于抗生素耐药性的传播特别重要。重复的、规则间隔的短回文重复序列(CRISPR)基因座赋予针对HLA-B的序列定向免疫。表皮葡萄球菌的临床分离株具有与几乎所有葡萄球菌接合质粒中存在的切口酶基因匹配的CRISPR间隔区。在这里,我们表明CRISPR干扰阻止了S.表皮的插入一个自我剪接的内含子到切口酶块干扰,尽管重组的靶序列在剪接的mRNA,表明干扰机制直接靶向DNA。我们得出结论,CRISPR基因座抵消了HGT的多种途径,可以限制病原菌抗生素耐药性的传播。
Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced short palindromic repeats (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate of Staphylococcus epidermidis harbors a CRISPR spacer that matches the nickase gene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation in S. epidermidis. Insertion of a self-splicing intron into nickase blocks interference despite the reconstitution of the target sequence in the spliced mRNA, indicating that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.
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