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Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation
Eliana Drenkard1, Frederick M Ausubel
1Department of Genetics, Harvard Medical School, Massahusetts General Hospital, Boston, MA 02114, USA.
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 populations. Pseudomonas aeruginosa infections generally persist despite the use of long-term antibiotic therapy. This has been explained by postulating that P. aeruginosa forms an antibiotic-resistant biofilm 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 itself. 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.
Insights
Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients are deadly. This study reveals antibiotic resistance and biofilm formation in CF lung infections are linked, driven by a protein called PvrR.
Area of Science:
- Microbiology
- Infectious Diseases
- Cystic Fibrosis Research
Background:
- Pseudomonas aeruginosa lung infections are a primary cause of mortality in cystic fibrosis (CF) patients.
- These infections often persist despite antibiotic treatment, with two main hypotheses: biofilm formation or selection of resistant variants.
Purpose of the Study:
- To investigate the relationship between antibiotic resistance and biofilm formation in Pseudomonas aeruginosa within the context of CF lung infections.
- To identify mechanisms regulating the switch between antibiotic-resistant and susceptible phenotypes.
Main Methods:
- In vitro and in vivo studies using CF patient lung samples.
- Phenotypic analysis of Pseudomonas aeruginosa variants.
- Identification and characterization of regulatory proteins involved in resistance and biofilm formation.
Main Results:
- Antibiotic-resistant phenotypic variants of P. aeruginosa with enhanced biofilm-forming capabilities arise frequently in CF lungs and in vitro.
- A regulatory protein, PvrR, was identified as controlling the transition between antibiotic-resistant and antibiotic-susceptible states.
- The findings indicate that antibiotic resistance and biofilm formation are interrelated phenomena in CF infections.
Conclusions:
- Both biofilm formation and the selection of resistant variants contribute to persistent Pseudomonas aeruginosa infections in CF.
- The PvrR protein is a key regulator of these adaptive processes.
- Targeting PvrR function presents a potential therapeutic strategy for treating CF-associated P. aeruginosa infections.
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