High prevalence of lasR-deficient Pseudomonas aeruginosa
occurring naturally in Cystic Fibrosis chronic lung infections has
been shown. However, mutational mechanisms acting on LasR
inactivation remain poorly investigated. We previously linked the
Mismatch Repair System-deficiency with the emergence of lasR
mutants, showing that lasR variants reproducibly emerge at a high
frequency from a hypermutator mutS strain. Here, we explored the
involvement of transient hypermutability in lasR mutagenesis by
studying the role of the error-prone DNA polymerase PolIV (dinB).
A dinB null mutant derived from a mutS strain was constructed and
the emergence of lasR variants was analyzed. Notably, dinB
disruption in a hypermutator background (mutSdinB) resulted in 3
fold increase (P=0.04) in the lasR emergence frequency respect to
the mutS strain. Furthermore, over-expression of PolIV in the
mutSdinB strain resulted in 16 fold decrease (P=0.04) in lasR
emergence. Analysis of the lasR mutational spectra in lasR variants
derived from the mutS strain, displayed that lasR inactivation was
entirely due to base substitutions (80% C-T transitions). In contrast,
20% of lasR variants emerged from the mutSdinB strain contained -1
frameshift and 80% base substitutions with only 38% being C-T
transitions. These results suggest that Pol IV could play an
antimutator role in lasR mutagenesis
