Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria
Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria
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DOI：
10.1039/b500182j
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Hergenrother, PJ
中科院分区：
文献类型：
--
作者：
DeNap, JCB;Hergenrother, PJ
现在常见的是细菌感染抵抗首选的抗生素治疗。特别地，对多种抗生素难治并最终导致患者死亡的医院获得性感染是普遍的。许多引起这些感染的细菌通过横向基因转移的过程对抗生素产生了耐药性，新获得的基因编码多种耐药性介导蛋白。这些外源基因通常通过质粒进入细菌，质粒是小的、环状的、染色体外的DNA片段。已经在几乎所有类别的抗生素和各种革兰氏阳性和革兰氏阴性生物体中观察到这种质粒编码的抗性;许多抗生素由于这种质粒编码的抗性而不再有效。从细菌中系统地去除这些介导耐药性的质粒将使细菌对标准抗生素重新敏感。因此，质粒提供了迄今为止尚未在临床上开发的新靶标。该观点详细介绍了质粒在多重耐药细菌中的作用，质粒控制其复制的机制，以及小分子破坏质粒复制和使细菌对抗生素重新敏感的潜力。重点放在质粒复制，是由小的反转录RNA介导的，和“质粒成瘾”系统，采用毒素和抗毒素。
It is now common for bacterial infections to resist the preferred antibiotic treatment. In particular, hospital- acquired infections that are refractory to multiple antibiotics and ultimately result in death of the patient are prevalent. Many of the bacteria causing these infections have become resistant to antibiotics through the process of lateral gene transfer, with the newly acquired genes encoding a variety of resistance- mediating proteins. These foreign genes often enter the bacteria on plasmids, which are small, circular, extrachromosomal pieces of DNA. This plasmid- encoded resistance has been observed for virtually all classes of antibiotics and in a wide variety of Gram-positive and Gram-negative organisms; many antibiotics are no longer effective due to such plasmid- encoded resistance. The systematic removal of these resistance- mediating plasmids from the bacteria would re-sensitize bacteria to standard antibiotics. As such, plasmids offer novel targets that have heretofore been unexploited clinically. This Perspective details the role of plasmids in multi-drug resistant bacteria, the mechanisms used by plasmids to control their replication, and the potential for small molecules to disrupt plasmid replication and re-sensitize bacteria to antibiotics. An emphasis is placed on plasmid replication that is mediated by small counter-transcript RNAs, and the " plasmid addiction" systems that employ toxins and antitoxins.