Elevated exopolysaccharide levels in Pseudomonas aeruginosa flagellar mutants have implications for biofilm growth and chronic infections

Autoři: Joe J. Harrison aff001;  Henrik Almblad aff001;  Yasuhiko Irie aff002;  Daniel J. Wolter aff002;  Heather C. Eggleston aff004;  Trevor E. Randall aff001;  Jacob O. Kitzman aff005;  Bethany Stackhouse aff005;  Julia C. Emerson aff006;  Sharon Mcnamara aff006;  Tyler J. Larsen aff002;  Jay Shendure aff005;  Lucas R. Hoffman aff002;  Daniel J. Wozniak aff004;  Matthew R. Parsek aff002
Působiště autorů: Department of Biological Sciences, University of Calgary, University Drive NW, Calgary, AB, Canada aff001;  Department of Microbiology, University of Washington, Seattle, Washington, United states of America aff002;  Department of Pediatrics, University of Washington, Seattle, Washington, United States of America aff003;  Department of Microbial Infection and Immunity, Department of Microbiology, Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, United States of America aff004;  Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America aff005;  Center for Clinical and Translational Research, Seattle Children’s Hospital, Seattle, Washington, United States of America aff006
Vyšlo v časopise: Elevated exopolysaccharide levels in Pseudomonas aeruginosa flagellar mutants have implications for biofilm growth and chronic infections. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008848
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008848


Pseudomonas aeruginosa colonizes the airways of cystic fibrosis (CF) patients, causing infections that can last for decades. During the course of these infections, P. aeruginosa undergoes a number of genetic adaptations. One such adaptation is the loss of swimming motility functions. Another involves the formation of the rugose small colony variant (RSCV) phenotype, which is characterized by overproduction of the exopolysaccharides Pel and Psl. Here, we provide evidence that the two adaptations are linked. Using random transposon mutagenesis, we discovered that flagellar mutations are linked to the RSCV phenotype. We found that flagellar mutants overexpressed Pel and Psl in a surface-contact dependent manner. Genetic analyses revealed that flagellar mutants were selected for at high frequencies in biofilms, and that Pel and Psl expression provided the primary fitness benefit in this environment. Suppressor mutagenesis of flagellar RSCVs indicated that Psl overexpression required the mot genes, suggesting that the flagellum stator proteins function in a surface-dependent regulatory pathway for exopolysaccharide biosynthesis. Finally, we identified flagellar mutant RSCVs among CF isolates. The CF environment has long been known to select for flagellar mutants, with the classic interpretation being that the fitness benefit gained relates to an impairment of the host immune system to target a bacterium lacking a flagellum. Our new findings lead us to propose that exopolysaccharide production is a key gain-of-function phenotype that offers a new way to interpret the fitness benefits of these mutations.

Klíčová slova:

Bacterial biofilms – Biofilms – Cystic fibrosis – Deletion mutation – Exopolysaccharides – Flagella – Phenotypes – Pseudomonas aeruginosa


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