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DNA聚合酶IV:抗细菌的潜在药靶
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国家重点研发计划(2019YFE0103900)


DNA polymerase IV: a potential target of drugs against bacteria
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    摘要:

    病原微生物及其耐药性是全球公共卫生的重要问题。众多人兽共患病原菌可通过食品产业链传播给人,同时耐药性使得感染更难治疗,增加了疾病传播和死亡的风险。从分子水平上研究病原体的变异规律、毒力及其致病机制有助于寻找新的药物靶点、研制新的药物。DNA聚合酶IV(polymerase IV,Pol IV)是γ家族聚合酶中的重要成员,广泛分布在原核生物、真核生物和古细菌3个生命域。Pol IV具有跨损伤DNA合成的能力,不仅在SOS反应(SOS response)和RpoS调控下响应DNA损伤,还参与细菌抗生素抗性及适应性的获得,在细菌中发挥着至关重要的作用。本文综述了近年来细菌Pol IV相关研究,回顾了其遗传特征、结构特征、表达调控及对细菌适应性的影响,并且讨论了Pol IV作为潜在药物靶点的可行性。

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    Pathogens and their drug resistance are key issues of global public health. Numerous zoonotic pathogens can be transmitted to humans through the food industry chain. Drug resistance makes infections more difficult to treat, increasing the risk of disease transmission and death. Studying the variation patterns, virulence, and pathogenic mechanisms of pathogens at the molecular level will help us to find new drug targets and developing new drugs. DNA polymerase IV (Pol IV), an important member of the γ family polymerases, is ubiquitous in the three life domains (prokaryotes, eukaryotes, and archaea). This enzyme is involved in the translesion DNA synthesis and plays a critical role in bacteria. It not only responds to DNA damage under SOS response and RpoS regulation but also is involved in the acquisition of antibiotic resistance and adaptation. This paper reviewed the recent studies related to bacterial Pol IV, including the genetic and structural features, expression regulation, and effects on bacterial adaptation, and discussed the feasibility of Pol IV as a potential drug target.

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吴小磊,贾程皓,王剑峰,王雷杰,乐敏. DNA聚合酶IV:抗细菌的潜在药靶[J]. 微生物学通报, 2022, 49(12): 5342-5358

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  • 收稿日期:2022-07-17
  • 最后修改日期:2022-08-09
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  • 在线发布日期: 2022-12-06
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