JAC Advance Access published online on February 6, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn044
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Original research |
Increased mutability of Pseudomonas aeruginosa in biofilms
Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
Received 21 November 2007; returned 15 January 2008; revised 4 January 2008; accepted 16 January 2008
* Corresponding author. Tel: +44-113-343-5604; Fax: +44-113-343-1407; E-mail: i.chopra{at}leeds.ac.uk
Objectives: Isolates of Pseudomonas aeruginosa from cystic fibrosis (CF) patients are frequently hypermutable due to selection of mutants with defects in DNA repair genes such as mutS. Since P. aeruginosa grows as a biofilm within the infected CF lung, it is possible that this mode of growth enhances the mutability of the organism thereby increasing the opportunity to derive permanent hypermutators through mutation in DNA repair genes. We have now conducted experiments to examine this possibility.
Methods: Using established procedures, we examined the mutability of P. aeruginosa PA01 in planktonic cultures and in biofilm cultures generated by growth in a Sorbarod system. Transcriptional profiling by DNA microarray was used to compare gene expression in planktonic and biofilm cells.
Results: Mutation frequency determinations for resistance to rifampicin and ciprofloxacin demonstrated that biofilm cultures of P. aeruginosa displayed up to a 105-fold increase in mutability compared with planktonic cultures. Several genes (ahpC, katA, sodB and PA3529, a probable peroxidase) that encode enzymes conferring protection against oxidative DNA damage were down-regulated in biofilm cells. In particular, katA, which encodes the major pseudomonal antioxidant catalase, was down-regulated 7.7-fold.
Conclusions: Down-regulation of antioxidant enzymes in P. aeruginosa biofilms may enhance the rate of mutagenic events due to the accumulation of DNA damage. Since P. aeruginosa forms biofilms in the CF lung, this mode of growth may enhance the direct selection of antibiotic-resistant organisms in CF patients and also increase the opportunity to derive permanent hypermutators thereby providing a further source of antibiotic-resistant mutants in the CF lung.
Key Words: mutation frequencies , microarrays , antibiotic resistance , hypermutators
Present address. Smith and Nephew Research Centre, York Science Park, Heslington, York YO10 5DF, UK.
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