title: Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Massahusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Drenkard
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D018441:Biofilms / Q000187:drug effects*; D003001:Cloning, Molecular; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007613:Kanamycin Resistance; D008168:Lung / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D012641:Selection, Genetic; D012965:Sodium Chloride / Q000494:pharmacology; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D012965:Sodium Chloride