Prediction of Burkholderia pseudomallei DsbA substrates identifies potential virulence factors and vaccine targets
| Autor: | Guillaume A. Petit, Jennifer L. Martin, Ben Vezina, Maria A. Halili |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Burkholderia pseudomallei Melioidosis Pathology and Laboratory Medicine Biochemistry Genome Virulence factor Substrate Specificity Medicine and Health Sciences Amino Acids Post-Translational Modification Francisella Genetics Multidisciplinary Bacterial Genomics biology Organic Compounds Gene Ontologies Microbial Genetics Genomics Francisella Tularensis Bacterial Pathogens Chemistry Medical Microbiology Bacterial Vaccines Physical Sciences Epitopes B-Lymphocyte Disulfide Bonds Medicine Pathogens Research Article Virulence Factors Science Virulence Microbial Genomics Microbiology Bacterial Proteins medicine Sulfur Containing Amino Acids Bacterial Genetics Amino Acid Sequence Cysteine Microbial Pathogens Francisella tularensis Sequence Homology Amino Acid Bacteria Organic Chemistry Chemical Compounds Organisms Biology and Life Sciences Proteins Computational Biology Bacteriology Periplasmic space biochemical phenomena metabolism and nutrition Genome Analysis biology.organism_classification medicine.disease bacterial infections and mycoses Gene Ontology DsbA biology.protein bacteria Genome Bacterial |
| Zdroj: | PLoS ONE, Vol 15, Iss 11, p e0241306 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Identification of bacterial virulence factors is critical for understanding disease pathogenesis, drug discovery and vaccine development. In this study we used two approaches to predict virulence factors ofBurkholderia pseudomallei, the Gram-negative bacterium that causes melioidosis.B.pseudomalleiis naturally antibiotic resistant and there are no clinically available melioidosis vaccines. To identifyB.pseudomalleiprotein targets for drug discovery and vaccine development, we chose to search for substrates of theB.pseudomalleiperiplasmic disulfide bond forming protein A (DsbA). DsbA introduces disulfide bonds into extra-cytoplasmic proteins and is essential for virulence in many Gram-negative organism, includingB.pseudomallei. The first approach to identifyB.pseudomalleiDsbA virulence factor substrates was a large-scale genomic analysis of 511 uniqueB.pseudomalleidisease-associated strains. This yielded 4,496 core gene products, of which we hypothesise 263 are DsbA substrates. Manual curation and database screening of the 263 mature proteins yielded 81 associated with disease pathogenesis or virulence. These were screened for structural homologues to predict potential B-cell epitopes. In the second approach, we searched theB.pseudomalleigenome for homologues of the more than 90 known DsbA substrates in other bacteria. Using this approach, we identified 15 putativeB.pseudomalleiDsbA virulence factor substrates, with two of these previously identified in the genomic approach, bringing the total number of putative DsbA virulence factor substrates to 94. The two putativeB.pseudomalleivirulence factors identified by both methods are homologues of PenI family β-lactamase and a molecular chaperone. These two proteins could serve as high priority targets for futureB.pseudomalleivirulence factor characterization. |
| Databáze: | OpenAIRE |
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