title: Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen ubiquitous to the natural environment but with the capability of moving to the host environment. Long-term infection of the airways of cystic fibrosis patients is associated with extensive genetic adaptation of P. aeruginosa, and we have studied cases of the initial stages of infection in order to characterize the early adaptive processes in the colonizing bacteria. A combination of global gene expression analysis and phenotypic characterization of longitudinal isolates from cystic fibrosis patients revealed well-known characteristics such as conversion to a mucoid phenotype by mucA mutation and increased antibiotic resistance by nfxB mutation. Additionally, upregulation of the atu operon leading to enhanced growth on leucine provides a possible example of metabolic optimization. A detailed investigation of the mucoid phenotype uncovered profound pleiotropic effects on gene expression including reduction of virulence factors and the Rhl quorum sensing system. Accordingly, mucoid isolates displayed a general reduction of virulence in the Caenorhabditis elegans infection model, altogether suggesting that the adaptive success of the mucoid variant extends beyond the benefits of alginate overproduction. In the overall perspective the global phenotype of the adapted variants appears to place them on paths in direction of fully adapted strains residing in long-term chronically infected patients.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Building 301, 2800 Lyngby, Denmark.
authors.forename: Martin Holm
authors.initials: MH
authors.lastname: Rau
authors.forename: Susse Kirkelund
authors.initials: SK
authors.lastname: Hansen
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Johansen
authors.forename: Line Elnif
authors.initials: LE
authors.lastname: Thomsen
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.forename: Kristian Fog
authors.initials: KF
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Jelsbak
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
mesh_terms: D000222:Adaptation, Physiological; D000464:Alginates / Q000378:metabolism; D000818:Animals; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D020723:Glucuronic Acid / Q000378:metabolism; D006603:Hexuronic Acids / Q000378:metabolism; D006801:Humans; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D012137:Respiratory System / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid