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A Fast and Reliable Pipeline for Bacterial Transcriptome Analysis Case study: Serine-dependent Gene Regulation in Streptococcus pneumoniae
Published on: April 25, 2015
A systematic strategy using a reconstructed genome-scale metabolic network for pathogen Streptococcuspneumoniae D39
Narges Pedram1, Hamid Rashedi1, Ehsan Motamedian2
1Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran, Iran.
Abstract:
Streptococcus pneumoniae is a Gram-positive bacterium that is one of the major causes of various infections such as pneumonia, meningitis, otitis media and endocarditis. Since antibiotic resistance of S. pneumoniae is pointed out as a challenge in the treatment of these infections, more studies are required to focus on disease prevention. In this research, a first manually curated genome-scale metabolic network of the pathogen S. pneumoniae D39 was reconstructed based on its genome annotation data, and biochemical knowledge from literature and databases. The model was validated by amino acid auxotrophies, gene essentiality analysis, and different carbohydrate sources. Then, a two-stage strategy was developed to find target genes for growth reduction of the pathogen and their importance in the various infection sites. In the first stage, growth-associated genes were identified by integration of transcriptomic data with the model and in the second stage, the importance of each gene in the metabolism for growth was evaluated using principal component analysis. The reports presented in the literature confirm the effect of some found genes on the growth of S. pneumoniae.
Insights
This study reconstructs a metabolic network for Streptococcus pneumoniae to identify genes crucial for pathogen growth, aiding in developing new prevention strategies against antibiotic-resistant infections.
Area of Science:
- Microbiology
- Systems Biology
- Metabolic Engineering
Background:
- Streptococcus pneumoniae causes severe infections like pneumonia and meningitis.
- Antibiotic resistance in S. pneumoniae necessitates novel disease prevention strategies.
- Understanding pathogen metabolism is key to developing targeted interventions.
Purpose of the Study:
- To reconstruct the first manually curated genome-scale metabolic network of Streptococcus pneumoniae D39.
- To develop a strategy for identifying essential genes for pathogen growth reduction.
- To evaluate the importance of identified genes in various infection sites.
Main Methods:
- Genome-scale metabolic network reconstruction using annotation and literature data.
- Model validation through auxotrophies, gene essentiality, and carbohydrate utilization.
- A two-stage strategy integrating transcriptomic data and principal component analysis to identify target genes.
Main Results:
- A validated genome-scale metabolic network for S. pneumoniae D39 was successfully reconstructed.
- A novel two-stage strategy identified potential target genes for growth reduction.
- The importance of identified genes in pathogen metabolism and infection sites was evaluated.
Conclusions:
- The reconstructed metabolic network provides a valuable platform for studying S. pneumoniae.
- The identified target genes offer potential avenues for novel therapeutic and preventive strategies.
- This systems biology approach advances our understanding of S. pneumoniae pathogenesis and antibiotic resistance challenges.
