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Published on: August 5, 2016
Genome-wide Core Proteome Analysis of Brucella melitensis Strains for Potential Drug Target Prediction
Noor Rahman1, Mohibullah Shah2, Ijaz Muhammad3
1Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan-23200, Pakistan.
Introduction:
Brucella melitensis is a facultative intracellular bacterial pathogen that causes abortion in goats and sheep and Malta fever in humans. In humans, chronic infection occurs through contact with infected animals or their waste products.
Methods:
The subtractive genomic approach is considered as a powerful and useful method for the identification of potential drug and vaccine targets. In this study, an attempt has been made through a subtractive proteomic strategy to identify novel drug targets in Brucella melitensis strains. Total 2604 core proteins of 56 strains of B. melitensis were taken, of which 545 non-human homologs were found to be essential for pathogen growth. Metabolic pathway analysis of these essential proteins revealed that 129 proteins are exclusively involved in 21 unique metabolic pathways in B. melitensis reference strain.
Results:
Of these, 31 proteins were found to be involved in 10 metabolic pathways that are unique to the pathogen. We selected Nitrate reductase subunit-β, Urease subunit α-2, Pantoate-β-alanine ligase, Isochorismatase, 2-dehydro-3-deoxyphosphooctonate aldolase and Serine O-acetyltransferase as drug targets in Brucella melitensis strains. Among these druggable targets, we selected only Pantoate-β- alanine ligase as high confidence target based on intensive literature curation, which is nonhomologous to the human gut metagenome involved in biosynthesis of secondary metabolites pathway. Pantothenate synthetase is the best chemotherapeutic target to combat Brucellulosis.
Conclusion:
Furthermore, in vitro and in vivo validation is needed for the evaluation of lead compounds against Brucella melitensis strains.
Insights
Researchers identified Pantoate-β-alanine ligase as a promising drug target to combat Brucella melitensis infections. This essential bacterial protein is crucial for pathogen survival and lacks human homologs, making it an ideal candidate for developing new treatments against brucellosis.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Drug Discovery
Background:
- Brucella melitensis causes significant animal and human diseases, including abortion in livestock and Malta fever in humans.
- Chronic human infections arise from contact with infected animals or their byproducts.
Purpose of the Study:
- To identify novel drug targets in Brucella melitensis using a subtractive proteomic strategy.
- To find essential proteins unique to the pathogen for therapeutic intervention.
Main Methods:
- A subtractive proteomic approach was employed, analyzing 2604 core proteins from 56 Brucella melitensis strains.
- Essential non-human homologous proteins were identified, followed by metabolic pathway analysis to pinpoint unique pathways.
Main Results:
- 129 essential proteins involved in 21 unique metabolic pathways were identified.
- 31 proteins in 10 pathogen-specific pathways were highlighted as potential drug targets.
- Pantoate-β-alanine ligase was selected as a high-confidence target due to its essentiality and lack of human homology.
Conclusions:
- Pantoate-β-alanine ligase, also known as Pantothenate synthetase, represents a promising chemotherapeutic target for brucellosis.
- Further in vitro and in vivo validation is required to evaluate lead compounds against Brucella melitensis.
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