Pangenome-wide and molecular evolution analyses of the Pseudomonas aeruginosa species
| Autor: | Alfonso Benítez-Páez, Sonia Cárdenas-Brito, Ana M. Rada-Bravo, Jeanneth Mosquera-Rendón, Eliana Restrepo-Pineda, Mauricio Corredor |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Genotype 030106 microbiology Genomics Human pathogen Bacterial genome size Biology medicine.disease_cause Genome Non-synonymous substitutions Evolution Molecular Pangenome 03 medical and health sciences Negative selection Phylogenetics Molecular evolution Genetics medicine Humans Pathogenicity Pseudomonas Infections Genetic variation Synonymous substitutions Gene Phylogeny Pseudomonas aeruginosa Biofilms Genome Bacterial Research Article Biotechnology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname BMC Genomics |
| Popis: | Background: Drug treatments and vaccine designs against the opportunistic human pathogen Pseudomonas aeruginosa have multiple issues, all associated with the diverse genetic traits present in this pathogen, ranging from multi-drug resistant genes to the molecular machinery for the biosynthesis of biofilms. Several candidate vaccines against P. aeruginosa have been developed, which target the outer membrane proteins; however, major issues arise when attempting to establish complete protection against this pathogen due to its presumably genotypic variation at the strain level. To shed light on this concern, we proposed this study to assess the P. aeruginosa pangenome and its molecular evolution across multiple strains. Results: The P. aeruginosa pangenome was estimated to contain more than 16,000 non-redundant genes, and approximately 15 % of these constituted the core genome. Functional analyses of the accessory genome indicated a wide presence of genetic elements directly associated with pathogenicity. An in-depth molecular evolution analysis revealed the full landscape of selection forces acting on the P. aeruginosa pangenome, in which purifying selection drives evolution in the genome of this human pathogen. We also detected distinctive positive selection in a wide variety of outer membrane proteins, with the data supporting the concept of substantial genetic variation in proteins probably recognized as antigens. Approaching the evolutionary information of genes under extremely positive selection, we designed a new Multi-Locus Sequencing Typing assay for an informative, rapid, and cost-effective genotyping of P. aeruginosa clinical isolates. Conclusions: We report the unprecedented pangenome characterization of P. aeruginosa on a large scale, which included almost 200 bacterial genomes from one single species and a molecular evolutionary analysis at the pangenome scale. Evolutionary information presented here provides a clear explanation of the issues associated with the use of protein conjugates from pili, flagella, or secretion systems as antigens for vaccine design, which exhibit high genetic variation in terms of non-synonymous substitutions in P. aeruginosa strains. The authors give thanks to the Colombian Agency for Science, Technology, and Innovation (Colciencias) and the National Fund for Science, Technology, and Innovation “Francisco José de Caldas” for grant 5817-5693-4856 to ABP and grant 1115-5693-3375 to ERP. The authors also thank the “Clinica Antioquia” microbiology laboratory staff, who donated the clinical isolates for the MLST studies. The JMR M.Sc. fellowship was supported by the Colombian Agency for Science, Technology, and Innovation (Colciencias) with funds of the 5817-5693-4856 grant. |
| Databáze: | OpenAIRE |
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