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Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation

Nature volume 416, pages 740–743 (2002)Cite this article

Abstract

Colonization of the lungs of cystic fibrosis (CF) patients by the opportunistic bacterial pathogen Pseudomonas aeruginosa is the principal cause of mortality in CF populations1,2. Pseudomonas aeruginosa infections generally persist despite the use of long-term antibiotic therapy1,3. This has been explained by postulating that P. aeruginosa forms an antibiotic-resistant biofilm4,5 consisting of bacterial communities embedded in an exopolysaccharide matrix. Alternatively, it has been proposed that resistant P. aeruginosa variants may be selected in the CF respiratory tract by antimicrobial therapy itself1,6. Here we report that both explanations are correct, and are interrelated. We found that antibiotic-resistant phenotypic variants of P. aeruginosa with enhanced ability to form biofilms arise at high frequency both in vitro and in the lungs of CF patients. We also identified a regulatory protein (PvrR) that controls the conversion between antibiotic-resistant and antibiotic-susceptible forms. Compounds that affect PvrR function could have an important role in the treatment of CF infections.

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Figure 1: Characterization of P. aeruginosa antibiotic-resistant RSCV.
Figure 2: Appearance of phenotypic variants resistant to kanamycin depends on environmental factors.
Figure 3: Identification and characterization of the P. aeruginosa PvrR response regulator.

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Acknowledgements

We thank J. Lai and R. A. Rogers for image analysis of biofilm structures; T. Mylonakis for help in obtaining the samples and clinical data from CF patients; M. J. Ferraro and K. Henry for providing the CF sputum samples; and M. Wildermuth for help analysing protein sequences. This work was supported by grants from Aventis SA and the National Institutes of Health.

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  1. Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Eliana Drenkard & Frederick M. Ausubel

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  1. Eliana Drenkard
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  2. Frederick M. Ausubel
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Correspondence to Frederick M. Ausubel.

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Competing interests

The work described in this manuscript was supported by Aventis SA, a pharmaceutical compnay. Although the data as described has no direct commercial application, it could be perceived that Aventis SA has a financial stake in the outcome of the experiments described. The authors have filed a patent application describing the work presented in this manuscript.

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Drenkard, E., Ausubel, F. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416, 740–743 (2002). https://doi.org/10.1038/416740a

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