Affiliation:
1. Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
Abstract
ABSTRACT
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 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 constructed and screened a library of random insertions in the PA14 strain. Some previously described
P. aeruginosa
and/or
Escherichia 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 showed higher spontaneous mutation rates than the wild-type strains, suggesting that PfpI plays a key role in DNA protection under nonstress conditions. Moreover, the inactivation of
pfpI
resulted in a dramatic increase in the H
2
O
2
-induced mutant frequency. Global transcription studies showed 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 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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
44 articles.
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