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一种用于复杂非结核分枝杆菌的新型单基因差异生物标志物。

A New Single Gene Differential Biomarker for Complex and Non-tuberculosis Mycobacteria.

作者信息

Zhou Lei, Ma Cuidie, Xiao Tongyang, Li Machao, Liu Haican, Zhao Xiuqin, Wan Kanglin, Wang Ruibai

机构信息

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

College of Pharmacy, Guizhou University, Guiyang, China.

出版信息

Front Microbiol. 2019 Aug 13;10:1887. doi: 10.3389/fmicb.2019.01887. eCollection 2019.

Abstract

BACKGROUND

Tuberculosis (TB) and non-tuberculous mycobacteriosis are serious threats to health worldwide. A simple non-sequencing method is needed for rapid diagnosis, especially in less experienced hospitals, but there is no specific biomarker commonly used for all mycobacteria. The gene of the prokaryotic error-prone non-homologous end joining system (NHEJ) has the potential to be a highly specific detection biomarker for mycobacteria.

METHODS

A total of 7294 mycobacterial genomes and 14 complete genomes of other families belonging to with were downloaded and analyzed for the existence and variation of the gene. complex (MTBC) and non-tuberculosis mycobacteria (NTM)- specific primers were designed and the actual amplification and identification efficiencies were tested with 150 strains of 40 species and 10 kinds of common respiratory pathogenic bacteria.

RESULTS

The gene of the NHEJ system was ubiquitous in all genome sequenced species and absent in other families of . On the one hand, as a single gene non-sequencing biomarker, its specific primers could effectively distinguish mycobacteria from other bacteria, MTBC from NTM, which would make the clinical detection of mycobacteria easy and have great clinical practical value. On the other hand, the sequence of gene can effectively distinguish NTM to species level with high resolution.

CONCLUSION

The Ku protein existed before the differentiation of species, which was an important protein involved in maintaining of the genome's integrity and related to the special growth stage of mycobacteria. It was rare in prokaryotes. These features made it a highly special differential biomarker for .

摘要

背景

结核病(TB)和非结核分枝杆菌病是全球健康的严重威胁。需要一种简单的非测序方法进行快速诊断,尤其是在经验较少的医院,但目前尚无适用于所有分枝杆菌的特异性生物标志物。原核易错非同源末端连接系统(NHEJ)的基因有潜力成为分枝杆菌的高度特异性检测生物标志物。

方法

下载并分析了总共7294个分枝杆菌基因组以及属于其他科的14个完整基因组,以研究该基因的存在和变异情况。设计了结核分枝杆菌复合群(MTBC)和非结核分枝杆菌(NTM)特异性引物,并使用40种分枝杆菌的150株菌株和10种常见呼吸道病原菌测试了实际扩增和鉴定效率。

结果

NHEJ系统的该基因在所有已测序基因组的分枝杆菌物种中普遍存在,而在其他科中不存在。一方面,作为一种单基因非测序生物标志物,其特异性引物可以有效区分分枝杆菌与其他细菌、MTBC与NTM,这将使分枝杆菌的临床检测变得容易,具有很大的临床实用价值。另一方面,该基因序列可以高分辨率地有效区分NTM至种水平。

结论

Ku蛋白在分枝杆菌物种分化之前就已存在,是参与维持基因组完整性的重要蛋白,与分枝杆菌的特殊生长阶段有关。它在原核生物中很少见。这些特性使其成为分枝杆菌高度特异的鉴别生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6780/6700215/0362cde58993/fmicb-10-01887-g001.jpg

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