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
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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. / Rau, Martin Holm; Hansen, Susse Kirkelund; Johansen, Helle Krogh; Thomsen, Line Elnif; Workman, Christopher T; Nielsen, Kristian Fog; Jelsbak, Lars; Høiby, Niels; Yang, Lei; Molin, Søren.
In: Environmental Microbiology, Vol. 12, No. 6, 01.06.2010, p. 1643-58.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 12
SP - 1643
EP - 1658
JO - Environmental Microbiology
JF - Environmental Microbiology
SN - 1462-2912
IS - 6
ER -
ID: 33918172