结核分枝杆菌抗原蛋白的研究及其应用新进展

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4 008个注释基因中(NC＿000 962.3, 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...

Effective antigens of Mycobacterium tuberculosis

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 4 008 annotated genes of MTB in NCBI (NC_000 962.3), 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.