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

TY - JOUR

T1 - 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

AU - Rau, Martin Holm

AU - Hansen, Susse Kirkelund

AU - Johansen, Helle Krogh

AU - Thomsen, Line Elnif

AU - Workman, Christopher T

AU - Nielsen, Kristian Fog

AU - Jelsbak, Lars

AU - Høiby, Niels

AU - Yang, Lei

AU - Molin, Søren

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

KW - Adaptation, Physiological

KW - Alginates

KW - Animals

KW - Child

KW - Cystic Fibrosis

KW - Gene Expression Regulation, Bacterial

KW - Glucuronic Acid

KW - Hexuronic Acids

KW - Humans

KW - Microarray Analysis

KW - Molecular Sequence Data

KW - Mutation

KW - Phenotype

KW - Pseudomonas Infections

KW - Pseudomonas aeruginosa

KW - Respiratory System

KW - Virulence

U2 - 10.1111/j.1462-2920.2010.02211.x

DO - 10.1111/j.1462-2920.2010.02211.x

M3 - Journal article

C2 - 20406284

SN - 1462-2912

VL - 12

SP - 1643

EP - 1658

JO - Environmental Microbiology

JF - Environmental Microbiology

IS - 6

ER -