结核分枝杆菌抗原蛋白的研究及其应用新进展  

Effective antigens of Mycobacterium tuberculosis

作　　者：陈莹[1,2] 徐平 戴二黑 张瑶[2] CHEN Ying;XU Ping;DAI Erhei;ZHANG Yao(Graduate School of Hebei Medical University,Shijiazhuang 050017,Hebei,China;State Key Laboratory of Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Research Unit of Proteomics&Research and Development of New Drug of Chinese Academy of Medical Sciences,Beijing Institute of Lifeomics,Academy of Military Medical Sciences of Academy of Military Science,Beijing 102206,China;The Fifth Hospital of Shijiazhuang,Hebei Medical University,Shijiazhuang 050021,Hebei,China)

机构地区：[1]河北医科大学研究生院,河北石家庄050017 [2]军事科学院军事医学研究院生命组学研究所、中国医学科学院蛋白质组学与药物研发新技术创新单元、国家蛋白质科学中心(北京)北京蛋白质组研究中心、蛋白质组学国家重点实验室,北京102206 [3]河北医科大学附属石家庄市第五医院,河北石家庄050021

出　　处：《微生物学报》2023年第8期2948-2966,共19页Acta Microbiologica Sinica

基　　金：京津冀基础研究合作专项(J200001);国家自然科学基金(32141003,31901037)。

摘　　要：结核病(tuberculosis,TB)是由结核分枝杆菌(Mycobacterium tuberculosis,MTB)感染引起的慢性传染病,是仅次于正在暴发的新型冠状病毒肺炎(COVID-19)的第二大单一感染致死病因。COVID-19的大流行对TB的诊断及治疗造成了破坏性的影响,全球实现终结TB目标的进展偏离了轨道。因此,早诊断、早治疗依然是防控TB蔓延的关键。TB精准诊断一直受MTB抗原特异性、检测技术特异性和灵敏度的影响,因此亟需挖掘高特异性新抗原、开发新检测技术。随着蛋白质基因组学(proteogenomics)和质谱技术的快速发展,从临床体液、组织样本中高效、精准靶向检测MTB特异性已知、甚至新抗原的表达,以及监测治疗过程中的抗原表达量的动态变化,是TB诊断及治疗的发展趋势。在MTB标准菌株H37Rv的4008个注释基因中(NC_000962.3,NCBI),国内外报道的已注释抗原虽有140多个,但仅有极少的抗原应用于TB的筛查及辅助诊断,离世界卫生组织(World Health Organization,WHO)的诊断标准尚远。本文通过对MTB已报道抗原以及基于蛋白质基因组学筛选特异性新抗原的潜力进行综述,为理解已知抗原及开发新抗原提供参考。Tuberculosis(TB),the second(after COVID-19)deadliest infectious killer,is caused by Mycobacterium tuberculosis(MTB).COVID-19 pandemic has shown devastating effect on the diagnosis and treatment of TB,posing a huge challenge to the ending of TB.Thus,early diagnosis and treatment is still the key to prevention and control of TB spread.The accurate diagnosis of TB depends on the specificity of MTB antigen and the specificity and sensitivity of detection techniques.Therefore,it is urgent to develop highly specific antigens and detection techniques.The advanced proteogenomics and mass spectrometry make it easy to detect known or new MTB-specific antigens from clinical body fluids and tissue samples and monitor the dynamic expression of antigen during treatment.Among 4008 annotated genes of MTB in NCBI(NC_000962.3),more than 140 known genes have been listed as potential antigens for TB diagnosis,while only a few annotated antigens have been used in the screening and auxiliary diagnosis of TB,which are still far from the WHO diagnostic standards.In this paper,we reviewed the reported antigens of MTB and the potential of screening specific neoantigens based on proteogenomic technologies for better understanding them and developing new efficient antigens.

关 键 词：结核分枝杆菌 结核病 诊断 抗原 血清学 蛋白质基因组学 

分 类 号：R378.911[医药卫生—病原生物学]