DNA损伤驱动布鲁氏锥虫抗原多样化
约翰斯·霍普金斯大学彭博公共卫生学院Monica R. Mugnier小组宣布他们研制了DNA损伤驱动布鲁氏锥虫抗原多样化。相关论文于2026年4月8日发表在《自然》杂志上。
在这里，课题组提出了一种高度敏感的靶向测序方法来测量VSG多样化。使用这种方法，该课题组人员证明了在VSG编码序列中Cas9诱导的DNA双链断裂可以诱导依赖RAD51和BRCA2的VSG重组，其模式与感染期间观察到的相同。这些新产生的VSGs在抗原性上不同于亲本克隆，它们能够促进免疫逃避。总之，这些结果提供了对VSG多样化机制的深入了解，并为研究病原微生物中抗原库的进化提供了实验框架。
研究人员表示，抗原变异，主题抗原编码基因的大基因组库，允许病原体逃避宿主抗体。许多病原体，包括非洲布鲁氏锥虫，通过基因组多样化扩展了它们的抗原库。尽管有证据表明，布鲁氏杆菌依赖于新的变异表面糖蛋白（VSG）基因的产生来维持慢性感染，但缺乏实验可处理的工具来研究这一过程，使其潜在机制模糊不清。
附：英文原文
Title: DNA damage drives antigen diversification in Trypanosoma brucei
Author: Smith, Jaclyn E., Wang, Kevin J., Kennedy, Erin M., Munday, Jane C., Singer, Lulu, Hakim, Jill M. C., So, Jaime, Beaver, Alexander K., Magesh, Aishwarya, Gilligan-Steinberg, Shane D., Zheng, Jessica, Zhang, Bailin, Moorthy, Dharani Narayan, Brown, Zachary E., Akin, Elgin Henry, Mwakibete, Lusajo, McCulloch, Richard, Mugnier, Monica R.
Issue&Volume: 2026-04-08
Abstract: Antigenic variation, using large genomic repertoires of antigen-encoding genes, allows pathogens to evade host antibody. Many pathogens, including the African trypanosome Trypanosoma brucei, extend their antigenic repertoire through genomic diversification. Although evidence suggests that T. brucei depends on the generation of new variant surface glycoprotein (VSG) genes to maintain a chronic infection1,2,3,4, a lack of experimentally tractable tools for studying this process has obscured its underlying mechanisms. Here we present a highly sensitive targeted sequencing approach for measuring VSG diversification. Using this method, we demonstrate that a Cas9-induced DNA double-strand break within the VSG coding sequence can induce RAD51- and BRCA2-dependent VSG recombination with patterns identical to those observed during infection. These newly generated VSGs are antigenically distinct from parental clones and thus capable of facilitating immune evasion. Together, these results provide insight into the mechanisms of VSG diversification and an experimental framework for studying the evolution of antigen repertoires in pathogenic microorganisms.
DOI: 10.1038/s41586-026-10337-6
Source: https://www.nature.com/articles/s41586-026-10337-6
期刊信息
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
投稿链接：http://www.nature.com/authors/submit_manuscript.html
