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BMC Genomics. 2015 Oct 30;16:883. doi: 10.1186/s12864-015-2069-0.

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

Author information

1
Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Children's Healthcare of Atlanta, Atlanta, GA, USA. jvarga@emory.edu.
2
Emory + Children's Center for Cystic Fibrosis Research, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA. jvarga@emory.edu.
3
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. jvarga@emory.edu.
4
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. mariette.barbier@gmail.com.
5
Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA. mariette.barbier@gmail.com.
6
Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma, de Mallorca, Spain. xavier.mulet@ssib.es.
7
Synthetic and Systems Biology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany. piotr.bielecki@yale.edu.
8
Present address: Immunobiology Department, Yale University, School of Medicine, New Haven, CT, 06511, USA. piotr.bielecki@yale.edu.
9
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. jagbartell@gmail.com.
10
Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Children's Healthcare of Atlanta, Atlanta, GA, USA. jpowings@gmail.com.
11
Emory + Children's Center for Cystic Fibrosis Research, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA. jpowings@gmail.com.
12
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. jpowings@gmail.com.
13
IUNICS, University of the Balearic Islands, Palma, de Mallorca, Spain. elbesodeldragon@hotmail.com.
14
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, University of Maryland, Baltimore, MD, USA. lhitt001@gmail.com.
15
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. michaelrdavisjr@gmail.com.
16
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. heathdamron@gmail.com.
17
Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA. heathdamron@gmail.com.
18
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. george.liechti.ctr@usuhs.edu.
19
Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma, de Mallorca, Spain. Puchalka@med.uni-muenchen.de.
20
Present address: Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany. Puchalka@med.uni-muenchen.de.
21
Systems and Synthetic Biology, Wageningen University, Wageningen, Netherlands. vitor.martinsdossantos@wur.nl.
22
Present address: Chair of Systems and Synthetic Biology, Wageningen University, Wageningen, The Netherlands. vitor.martinsdossantos@wur.nl.
23
Present address: LifeGlimmer GmbH, Berlin, Germany. vitor.martinsdossantos@wur.nl.
24
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, University of Maryland, Baltimore, MD, USA. Rkernst@umaryland.edu.
25
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. papin@virginia.edu.
26
IUNICS, University of the Balearic Islands, Palma, de Mallorca, Spain. sebastian.alberti@uib.es.
27
Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma, de Mallorca, Spain. antonio.oliver@ssib.es.
28
Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Children's Healthcare of Atlanta, Atlanta, GA, USA. joanna.goldberg@emory.edu.
29
Emory + Children's Center for Cystic Fibrosis Research, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA. joanna.goldberg@emory.edu.
30
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. joanna.goldberg@emory.edu.

Abstract

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 ~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.

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.

PMID:
26519161
PMCID:
PMC4628258
DOI:
10.1186/s12864-015-2069-0
[Indexed for MEDLINE]
Free PMC Article

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