Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients

D.A. D'Argenio, M.H. Wu, L.R. Hoffman, H.D. Kulasekara, E. Deziel, E.E. Smith, H. Nguyen, R.K. Ernst, T.J.L. Freeman, D.H. Spencer, M. Brittnacher, H.S. Hayden, S. Selgrade, Mikkel Klausen, D.R. Goodlett, J.L. Burns, B.W. Ramsey, S.I. Miller

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    Abstract

    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 beta-lactamase activity that increased tolerance to ceftazidime, a widely used beta-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.
    Original languageEnglish
    JournalMolecular Microbiology
    Volume64
    Issue number2
    Pages (from-to)512-533
    ISSN0950-382X
    DOIs
    Publication statusPublished - 2007

    Cite this

    D'Argenio, D. A., Wu, M. H., Hoffman, L. R., Kulasekara, H. D., Deziel, E., Smith, E. E., Nguyen, H., Ernst, R. K., Freeman, T. J. L., Spencer, D. H., Brittnacher, M., Hayden, H. S., Selgrade, S., Klausen, M., Goodlett, D. R., Burns, J. L., Ramsey, B. W., & Miller, S. I. (2007). Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Molecular Microbiology, 64(2), 512-533. https://doi.org/10.1111/j.1365-2958.2007.05678.x