Mycobacterium tuberculosis effectors involved in host–pathogen interaction revealed by a multiple scales integrative pipeline

IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES
Wu Li , Xiangyu Fan , Quanxin Long , Longxiang Xie , Jianping Xie
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引用次数: 13

Abstract

Background

Mycobacterium tuberculosis (Mtb) has evolved multiple strategies to counter host immunity. Proteins are one important player in the host–pathogen interaction. A comprehensive list of such proteins will benefit our understanding of pathogenesis of Mtb.

Methods

A genome-scale dataset was created from different sources of published data: global gene expression studies in disease models; genome-wide insertional mutagenesis defining gene essentiality under different conditions; genes lost in clinical isolates; subcellular localization analysis and non-homology analysis. Using data mining and meta-analysis, expressed proteins critical for intracellular survival of Mtb are first identified, followed by subcellular localization analysis, finally filtering a series of subtractive channel of analysis to find out promising drug target candidates.

Results

The analysis found 54 potential candidates essential for the intracellular survival of the pathogen and non-homologous to host or gut flora, and might be promising drug targets.

Conclusion

Based on our meta-analysis and bioinformatics analysis, 54 hits were found from Mtb around 4000 open reading frames. These hits can be good candidates for further experimental investigation.

多尺度整合管道揭示结核分枝杆菌效应物参与宿主-病原体相互作用
背景结核分枝杆菌(Mtb)已经进化出多种对抗宿主免疫的策略。蛋白质是宿主-病原体相互作用的重要参与者。这些蛋白质的全面列表将有助于我们了解结核分枝杆菌的发病机制。方法从不同来源的已发表数据中创建基因组规模数据集:疾病模型中的全球基因表达研究;全基因组插入突变确定不同条件下基因的必要性临床分离株基因丢失;亚细胞定位分析和非同源性分析。通过数据挖掘和荟萃分析,首先鉴定出Mtb细胞内存活的关键表达蛋白,然后进行亚细胞定位分析,最后过滤一系列的减法分析通道,找到有希望的药物候选靶点。结果分析发现54种对病原菌的细胞内存活至关重要且与宿主或肠道菌群非同源的潜在候选药物,可能是有希望的药物靶点。结论基于meta分析和生物信息学分析,从4000个开放阅读框中发现了54个点击率。这些撞击可以作为进一步实验研究的良好候选者。
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来源期刊
Infection Genetics and Evolution
Infection Genetics and Evolution 医学-传染病学
CiteScore
8.40
自引率
0.00%
发文量
215
审稿时长
82 days
期刊介绍: (aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID) Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance. However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors. Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases. Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .
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