Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression.
BACKGROUND
Pseudomonas aeruginosa with mutations in the transcriptional regulator LasR chronically infect the airways of people with cystic fibrosis (CF), yet the prevalence and clinical implications of lasR mutant infection are unknown.


METHODS
In an exploratory study, we screened 166 P. aeruginosa isolates from 58 CF patients for LasR inactivation and mucoidy, and compared clinical characteristics among source patients.


RESULTS
lasR mutation prevalence was comparable to that of mucoidy, the best-described CF-adapted phenotype, but affected patients were on average approximately 2 years younger. In a regression analysis, lung function decline with age was worse among patients with lasR mutant infection than in those without, similar to the effect of mucoidy.


CONCLUSIONS
Culture positivity for lasR mutant P. aeruginosa may serve as a marker of early CF adaptive change of prognostic significance. Furthermore, as LasR inactivation alters susceptibility to antibiotics, infection with lasR mutant P. aeruginosa may impact response to therapy.
Hoffman
Lucas R
LR
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA. lhoffm@u.washington.edu
Kulasekara
Hemantha D
HD
Emerson
Julia
J
Houston
Laura S
LS
Burns
Jane L
JL
Ramsey
Bonnie W
BW
Miller
Samuel I
SI
D000367:Age Factors; D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011552:Pseudomonas Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000235:genetics; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D015534:Trans-Activators / Q000235:genetics*
D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators