ArticleThe Journal of biological chemistry2011
Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.Infection and immunity · 2025Review
- AProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Host-directed therapy against tuberculosis: Concept and recent developments.Journal of biosciences · 2023Review
- Measurement of Autophagy Activity Reveals Time-Dependent, Bacteria-Specific Turnover duringPathogens (Basel, Switzerland) · 2022Article
- Dysregulated expression of microRNAs in aqueous humor from intraocular tuberculosis patients.Molecular biology reports · 2022Article
- Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan.Military Medical Research · 2021Article
- Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis.Nature communications · 2020Article
- NetConfer: a web application for comparative analysis of multiple biological networks.BMC biology · 2020Article
- Down-Regulation of miR-378d Increased Rab10 Expression to Help Clearance ofFrontiers in cellular and infection microbiology · 2020Article
- RegX3 ActivatesFrontiers in microbiology · 2020Article
- The humoral immune response is essential for successful vaccine protection against paratuberculosis in sheep.BMC veterinary research · 2019Article
- Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species.Free radical biology & medicine · 2019Article
- MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy.Nature communications · 2018Article
- Alternate splicing of transcripts upon Mycobacterium tuberculosis infection impacts the expression of functional protein domains.IUBMB life · 2018Article
- Integrated Multi-Omic Analysis ofFrontiers in microbiology · 2018Article
- Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis.Science immunology · 2017Article
- Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection.PLoS pathogens · 2017Article
- CompNet: a GUI based tool for comparison of multiple biological interaction networks.BMC bioinformatics · 2016Article
- Mycobacterium tuberculosis WhiB3 Responds to Vacuolar pH-induced Changes in Mycothiol Redox Potential to Modulate Phagosomal Maturation and Virulence.The Journal of biological chemistry · 2016Article
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Authors and funding
7 authors.
Funding
Abstract
Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbiased manner. The analysis superimposes differentially regulated genes between contrasting environments onto the network of functional protein associations followed by a series of iterative enrichments and network analysis. To test the utility of the approach, we infected THP1 macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the attenuated non-virulent strain H37Ra as contrasting perturbations and generated the temporal global expression profiles. EPA of the results provided details of response-specific and time-dependent host molecular network perturbations. Further analysis identified tyrosine kinase Src as the major regulatory hub discriminating the responses between wild-type and attenuated Mtb infection. We were then able to verify this novel role of Src experimentally and show that Src executes its role through regulating two vital antimicrobial processes of the host cells (i.e. autophagy and acidification of phagolysosome). These results bear significant potential for developing novel anti-tuberculosis therapy. We propose that EPA could prove extremely useful in understanding complex cellular responses for a variety of perturbations, including pathogenic infections.
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