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Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC). Madrid, Spain
Hypermutator Pseudomonas aeruginosa strains, characterized by an increased spontaneous mutation rate, are found at high frequencies in chronic lung infections. Hypermutability is associated with the loss of antimutator genes related to DNA-repair or damage avoidance systems. Only a few antimutator genes have already been described in P. aeruginosa, although there is some evidence that additional genes may be involved in naturally-occurring hypermutability. In order to find new P. aeruginosa antimutator genes, we have constructed and screened a library of random insertions in the PA14 strain. Some previously described P. aeruginosa and/or E. coli antimutator genes such as mutS, mutL, uvrD, mutT, ung, and mutY were detected, indicating a good coverage of our insertional library. One additional mutant contained an insertion in the P. aeruginosa PA14-04650 (pfpI) gene, putatively encoding a member of the DJ-1/ThiJ/PfpI superfamily, which includes chaperones, peptidases, and the Parkinson's disease protein DJ-1a. The pfpI defective mutants in both PAO1 and PA14 show higher spontaneous mutation rates than the wild-type strains, suggesting that PfpI plays a key role in DNA protection under non-stress conditions. Moreover, the inactivation of pfpI results in a dramatic increase in the H2O2-induced mutant frequency. Global transcription studies show the induction of bacteriophage Pf1 genes and the repression of genes related to iron metabolism, suggesting that the increased spontaneous mutant frequency may be due to a reduced protection against the basal level of reactive oxygen species. Finally, pfpI mutants are more sensitive to different types of stress and are affected in biofilm formation.
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
The Pseudomonas aeruginosa pfpI gene plays an antimutator role and provides general stress protection
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Abstract
| Appl. Environ. Microbiol. | Infect. Immun. | Eukaryot. Cell |
|---|---|---|
| Mol. Cell. Biol. | J. Virol. | Microbiol. Mol. Biol. Rev. |
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