Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20156
Título
Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains
Autor(es)
Varga, John J | Barbier, Mariette | Mulet, Xavier | Bielecki, Piotr | Bartell, Jennifer A | Owings, Joshua P | Martinez-Ramos, Inmaculada | Hittle, Lauren E | Davis, Michael R., Jr | Damron, F. Heath | Liechti, George W | Puchalka, Jacek | dos Santos, Vitor Martins | Ernst, Robert K | Papin, Jason A | Alberti, Sebastian | Oliver, Antonio | Goldberg, Joanna B.
Fecha de publicación
2015-10-30
Cita
Varga JJ, Barbier M, Mulet Aguilá FJ, Bielecki P, Bartell JA, Owings JP, et al. Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains. BMC Genomics. 2015 Oct 30;16:883.
Idioma
Inglés
Tipo de documento
research article
Resumen
Background: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify mechanisms responsible for adaptation during bronchiectasis infections, a bronchiectasis isolate, PAHM4, was phenotypically and genotypically characterized. Results: This strain displays phenotypes that have been associated with chronic respiratory infections in CF including alginate over-production, rough lipopolysaccharide, quorum-sensing deficiency, loss of motility, decreased protease secretion, and hypermutation. Hypermutation is a key adaptation of this bacterium during the course of chronic respiratory infections and analysis indicates that PAHM4 encodes a mutated mutS gene responsible for a similar to 1,000-fold increase in mutation rate compared to wild-type laboratory strain P. aeruginosa PAO1. Antibiotic resistance profiles and sequence data indicate that this strain acquired numerous mutations associated with increased resistance levels to b-lactams, aminoglycosides, and fluoroquinolones when compared to PAO1. Sequencing of PAHM4 revealed a 6.38 Mbp genome, 5.9 % of which were unrecognized in previously reported P. aeruginosa genome sequences. Transcriptome analysis suggests a general down-regulation of virulence factors, while metabolism of amino acids and lipids is up-regulated when compared to PAO1 and metabolic modeling identified further potential differences between PAO1 and PAHM4. Conclusions: This work provides insights into the potential differential adaptation of this bacterium to the lung of patients with bronchiectasis compared to other clinical settings such as cystic fibrosis, findings that should aid the development of disease-appropriate treatment strategies for P. aeruginosa infections.
Palabras clave
Pseudomonas aeruginosa | Metabolic model | Transcriptome | Comparative genomics | Cystic fibrosis | Bronchiectasis
MESH
Genotype | Anti-Bacterial Agents | Secondary Metabolism | Microbial Sensitivity Tests | Molecular Sequence Data | Alleles | Humans | Cystic Fibrosis | Adaptation, Biological | Phenotype | High-Throughput Nucleotide Sequencing | Quorum Sensing | Pseudomonas aeruginosa | Chronic Disease | Pseudomonas Infections | Bacterial Proteins | Bronchiectasis | Genome, Bacterial | Biofilms | Computational Biology | Drug Resistance, Bacterial | Transcriptome | Mutation Rate | Mutation | Gene Expression Profiling | Gene Order | Genomics | Virulence
DECS
Metabolismo Secundario | Enfermedad Crónica | Virulencia | Orden Génico | Genómica | Proteínas Bacterianas | Bronquiectasia | Perfilación de la Expresión Génica | Tasa de Mutación | Transcriptoma | Farmacorresistencia Bacteriana | Mutación | Alelos | Fibrosis Quística | Percepción de Quorum | Adaptación Biológica | Pruebas de Sensibilidad Microbiana | Datos de Secuencia Molecular | Humanos | Genotipo | Fenotipo | Secuenciación de Nucleótidos de Alto Rendimiento | Biología Computacional | Infecciones por Pseudomonas | Pseudomonas aeruginosa | Antibacterianos | Genoma Bacteriano | Biopelículas
Versión en línea
DOI
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