Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains

BMC Genomics

Research Article

Jennifer A. Bartell¹  Jason A. Papin¹  Robert K. Ernst²  Lauren E. Hittle²  Michael R. Davis³  George W. Liechti³  Mariette Barbier⁴  F. Heath Damron⁴  Joshua P. Owings⁵  Joanna B. Goldberg⁵  John J. Varga⁵  Sebastian Albertí⁶  Inmaculada Martinez-Ramos⁶  Xavier Mulet⁷  Antonio Oliver⁷  Jacek Puchałka⁸  Piotr Bielecki⁹  Vitor A. P. Martins dos Santos^1,10 

[1] Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA;Department of Microbial Pathogenesis, University of Maryland School of Dentistry, University of Maryland, Baltimore, MD, USA;Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA;Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA;Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA;Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Children’s Healthcare of Atlanta, Atlanta, GA, USA;Emory + Children’s Center for Cystic Fibrosis Research, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA;Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA;IUNICS, University of the Balearic Islands, Palma, de Mallorca, Spain;Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma, de Mallorca, Spain;Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma, de Mallorca, Spain;Present address: Dr. von Hauner Children’s Hospital, Ludwig Maximilians University, Munich, Germany;Synthetic and Systems Biology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany;Present address: Immunobiology Department, Yale University, School of Medicine, 06511, New Haven, CT, USA;Systems and Synthetic Biology, Wageningen University, Wageningen, Netherlands;Present address: Chair of Systems and Synthetic Biology, Wageningen University, Wageningen, The Netherlands;Present address: LifeGlimmer GmbH, Berlin, Germany;

关键词: Pseudomonas aeruginosa;    Metabolic model;    Transcriptome;    Comparative genomics;    Cystic fibrosis;    Bronchiectasis;   

DOI  :  10.1186/s12864-015-2069-0

 received in 2015-05-21, accepted in 2015-10-03,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPseudomonas 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.ResultsThis 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 ~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 β-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.ConclusionsThis 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.

【 授权许可】

CC BY   
© Varga et al. 2015