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Genetics-directed drug discovery for combating Mycobacterium tuberculosis infection
- Source :
- Journal of Biomolecular Structure and Dynamics. 35:616-621
- Publication Year :
- 2016
- Publisher :
- Informa UK Limited, 2016.
-
Abstract
- Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis (TB), is one of the most infectious bacteria in the world. The traditional strategy to combat TB involves targeting the pathogen directly; however, the rapid evolution of drug resistance lessens the efficiency of this anti-TB method. Therefore, in recent years, some researchers have turned to an alternative anti-TB strategy, which hinders Mtb infection through targeting host genes. In this work, using a theoretical genetic analysis, we identified 170 Mtb infection-associated genes from human genetic variations related to Mtb infection. Then, the agents targeting these genes were identified to have high potential as anti-TB drugs. In particular, the agents that can target multiple Mtb infection-associated genes are more druggable than the single-target counterparts. These potential anti-TB agents were further screened by gene expression data derived from connectivity map. As a result, some agents were revealed to have high interest for experimental evaluation. This study not only has important implications for anti-TB drug discovery, but also provides inspirations for streamlining the pipeline of modern drug discovery.
- Subjects :
- 0301 basic medicine
Tuberculosis
Pharmacogenomic Variants
Antitubercular Agents
Druggability
Drug resistance
Mycobacterium tuberculosis
03 medical and health sciences
Bacterial Proteins
Structural Biology
Drug Discovery
Drug Resistance, Bacterial
medicine
Humans
Genetic Predisposition to Disease
Molecular Biology
Pathogen
Genetics
biology
Drug discovery
Gene Expression Profiling
Gene Expression Regulation, Bacterial
General Medicine
biology.organism_classification
medicine.disease
Gene expression profiling
030104 developmental biology
Subjects
Details
- ISSN :
- 15380254 and 07391102
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Biomolecular Structure and Dynamics
- Accession number :
- edsair.doi.dedup.....e645397eb3e3d65de1761b5a923474c1