DNA聚合酶Ⅳ:抗细菌的潜在药靶  

DNA polymeraseⅣ:a potential target of drugs against bacteria

作　　者：吴小磊 贾程皓 王剑峰[3] 王雷杰 乐敏[1,2,4] WU Xiaolei;JIA Chenghao;WANG Jianfeng;WANG Leijie;YUE Min(Molecular Microbiology and Food Safety Laboratory,Institute of Preventive Veterinary Medicine,Zhejiang University,Zhejiang Province Key Laboratory of Preventive Veterinary Medicine,Hangzhou 310058,Zhejiang,China;Hainan Institute of Zhejiang University,Sanya 572025,Hainan,China;Hangzhou Original Breeding Farm,Hangzhou 311115,Zhejiang,China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,Zhejiang,China)

机构地区：[1]浙江大学动物预防医学研究所分子微生物学与食品安全实验室浙江省动物预防医学重点实验室,浙江杭州310058 [2]海南浙江大学研究院,海南三亚572025 [3]杭州市原种场,浙江杭州311115 [4]浙江大学医学院附属第一医院传染病诊治国家重点实验室,浙江杭州310003

出　　处：《微生物学通报》2022年第12期5342-5358,共17页Microbiology China

基　　金：国家重点研发计划(2019YFE0103900)。

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(polymeraseⅣ,PolⅣ)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。PolⅣ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PolⅣ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PolⅣ作为潜在药物靶点的可行性。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 polymeraseⅣ(PolⅣ),an important member of theγfamily 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 PolⅣ,including the genetic and structural features,expression regulation,and effects on bacterial adaptation,and discussed the feasibility of PolⅣas a potential drug target.

关 键 词：DNA聚合酶Ⅳ 抗菌药物 抗生素 

分 类 号：TS201.3[轻工技术与工程—食品科学]