D'Argenio, David A; Wu, Manhong; Hoffman, Lucas R.; Kulasekara, Hemantha D; Déziel, Éric; Smith, Eric E; Nguyen, Hai; Ernst, Robert K; Larson Freeman, Theodore J; Spencer, David H; Brittnacher, Mitchell; Hayden, Hillary S; Selgrade, Sara; Klausen, Mikkel; Goodlett, David R; Burns, Jane L. ; Ramsey, Bonnie W. ; Miller, Samuel I
(2007).
Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients
Molecular Microbiology
, vol. 64
, nº 2.
p. 512-533.
DOI: 10.1111/j.1365-2958.2007.05678.x.
Résumé
The opportunistic pathogen Pseudomonas aeruginosa undergoes genetic change during chronic
airway infection of cystic fibrosis (CF) patients. One common change is a mutation inactivating
lasR, which encodes a transcriptional regulator that responds to a homoserine lactone signal to
activate expression of acute virulence factors. Colonies of lasR mutants visibly accumulated the
iridescent intercellular signal 4-hydroxy-2-heptylquinoline. Using this colony phenotype, we
identified P. aeruginosa lasR mutants that emerged in the airway of a CF patient early during chronic
infection, and during growth in the laboratory on a rich medium. The lasR loss-of-function mutations
in these strains conferred a growth advantage with particular carbon and nitrogen sources, including
amino acids, in part due to increased expression of the catabolic pathway regulator CbrB. This growth
phenotype could contribute to selection of lasR mutants both on rich medium and within the CF
airway, supporting a key role for bacterial metabolic adaptation during chronic infection. Inactivation
of lasR also resulted in increased β-lactamase activity that increased tolerance to ceftazidime, a
widely used β-lactam antibiotic. Loss of LasR function may represent a marker of an early stage in
chronic infection of the CF airway with clinical implications for antibiotic resistance and disease
progression
Type de document: |
Article
|
Mots-clés libres: |
QUORUM-SENSING INHIBITORS, TO-CELL COMMUNICATION, WILD-TYPE STRAINS, STATIONARY-PHASE, ANTIMICROBIAL RESISTANCE, STAPHYLOCOCCUS-AUREUS, PULMONARY INFECTION, GENETIC ADAPTATION, QUINOLONE SIGNAL, BETA-LACTAMASES |
Centre: |
Centre INRS-Institut Armand Frappier |
Date de dépôt: |
01 mai 2014 18:03 |
Dernière modification: |
01 mai 2014 18:03 |
URI: |
http://espace.inrs.ca/id/eprint/2233 |
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