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oai:repisalud.isciii.es:20.500.12105/201562024-11-29T01:36:37Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Varga, John J author Barbier, Mariette author Mulet, Xavier author Bielecki, Piotr author Bartell, Jennifer A author Owings, Joshua P author Martinez-Ramos, Inmaculada author Hittle, Lauren E author Davis, Michael R., Jr author Damron, F. Heath author Liechti, George W author Puchalka, Jacek author dos Santos, Vitor Martins author Ernst, Robert K author Papin, Jason A author Alberti, Sebastian author Oliver, Antonio author Goldberg, Joanna B. author 2015-10-30 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. 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. 1471-2164 http://hdl.handle.net/20.500.13003/10656 http://hdl.handle.net/20.500.12105/20156 26519161 10.1186/s12864-015-2069-0 BMC Genomics 2-s2.0-84945561988 365279000002 L606639182 Pseudomonas aeruginosa Metabolic model Transcriptome Comparative genomics Cystic fibrosis Bronchiectasis Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains