Abstract
Fatty acid biosynthesis of Mycobacterium tuberculosis was analyzed using graph theory and influential (impacting) proteins were identified. The graphs (digraphs) representing this biological network provide information concerning the connectivity of each protein or metabolite in a given pathway, providing an insight into the importance of various components in the pathway, and this can be quantitatively analyzed. Using a graph theoretic algorithm, the most influential set of proteins (sets of {1, 2, 3}, etc.), which when eliminated could cause a significant impact on the biosynthetic pathway, were identified. This set of proteins could serve as drug targets. In the present study, the metabolic network of Mycobacterium tuberculosis was constructed and the fatty acid biosynthesis pathway was analyzed for potential drug targeting. The metabolic network was constructed using the KEGG LIGAND database and subjected to graph theoretical analysis. The nearness index of a protein was used to determine the influence of the said protein on other components in the network, allowing the proteins in a pathway to be ordered according to their nearness indices. A method for identifying the most strategic nodes to target for disrupting the metabolic networks is proposed, aiding the development of new drugs to combat this deadly disease.
Highlights
The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analyzed, improving understanding of the biology of this slow-growing pathogen and aiding the development of new prophylactic and therapeutic interventions [1]
Drug resistance follows inadequate compliance, and AIDS patients with a weakened immune system are very susceptible to M. tuberculosis and it is a common cause of death [3]
Data for assessing the pathway are available in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database and were used to obtain a flowchart of the fatty acid biosynthesis pathway of Mycobacterium tuberculosis H37Rv
Summary
The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analyzed, improving understanding of the biology of this slow-growing pathogen and aiding the development of new prophylactic and therapeutic interventions [1]. Analyzing a wellconnected cluster of proteins linked to several pathways enables the specific pathway concerned with mycolic acid synthesis to be targeted [3]. The bacterium possesses a thick layer of lipid on the outer surface that protects it from noxious chemicals and the host’s immune system [3]; these lipids are present in the CorynebacteriumMycobacterium-Nocardia group. They give rise to important characteristics including resistance to chemical injury and dehydration, low permeability to antibiotics, virulence, acid-fast staining and the ability to persist within a host. Drug resistance follows inadequate compliance, and AIDS patients with a weakened immune system are very susceptible to M. tuberculosis and it is a common cause of death [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
