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志贺分枝杆菌基因组和宿主细胞反应的景观揭示了其致病特征。

Landscape of the genome and host cell response of Mycobacterium shigaense reveals pathogenic features.

机构信息

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China.

出版信息

Emerg Microbes Infect. 2018 Jun 22;7(1):112. doi: 10.1038/s41426-018-0116-z.

DOI:10.1038/s41426-018-0116-z
PMID:29934568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6015043/
Abstract

A systems approach was used to explore the genome and transcriptome of Mycobacterium shigaense, a new opportunistic pathogen isolated from a patient with a skin infection, and the host response transcriptome was assessed using a macrophage infection model. The M. shigaense genome comprises 5,207,883 bp, with 67.2% G+C content and 5098 predicted coding genes. Evolutionarily, the bacterium belongs to a cluster in the phylogenetic tree along with three target opportunistic pathogenic strains, namely, M. avium, M. triplex and M. simiae. Potential virulence genes are indeed expressed by M. shigaense under culture conditions. Phenotypically, M. shigaense had similar infection and replication capacities in a macrophage model as the opportunistic species compared to M. tuberculosis. M. shigaense activated NF-κB, TNF, cytokines and chemokines in the host innate immune-related signaling pathways and elicited an early response shared with pathogenic bacilli except M. tuberculosis. M. shigaense upregulated specific host response genes such as TLR7, CCL4 and CXCL5. We performed an integrated and comparative analysis of M. shigaense. Multigroup comparison indicated certain differences with typical pathogenic bacilli in terms of gene features and the macrophage response.

摘要

采用系统方法探索了从皮肤感染患者中分离出来的新型机会性病原体——耻垢分枝杆菌的基因组和转录组,并使用巨噬细胞感染模型评估了宿主应答转录组。耻垢分枝杆菌的基因组由 5207883bp 组成,G+C 含量为 67.2%,预测有 5098 个编码基因。从进化角度来看,该细菌属于与三个目标机会性病原体(鸟分枝杆菌、三亲分枝杆菌和猿分枝杆菌)在系统发育树上聚类的一组。耻垢分枝杆菌在培养条件下确实表达潜在的毒力基因。表型上,与结核分枝杆菌相比,耻垢分枝杆菌在巨噬细胞模型中的感染和复制能力与机会性病原体相似。耻垢分枝杆菌在宿主固有免疫相关信号通路中激活 NF-κB、TNF、细胞因子和趋化因子,并引起与致病性杆菌(除结核分枝杆菌外)共享的早期反应。耻垢分枝杆菌上调了 TLR7、CCL4 和 CXCL5 等特定的宿主反应基因。我们对耻垢分枝杆菌进行了综合和比较分析。多组比较表明,与典型的致病性杆菌相比,在基因特征和巨噬细胞反应方面存在某些差异。

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本文引用的文献

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