The small DdrR protein directly interacts with the UmuDAb regulator to inhibit the mutagenic DNA damage response in Acinetobacter baumannii

Acinetobacter baumannii poses a great threat in healthcare settings worldwide with clinical isolates revealing an ever evolving multidrug-resistance. Here, we report the molecular mechanisms governing the tight repression of the error-prone DNA polymerase umuDC genes in this important bacterial human pathogen. We demonstrate that the small DdrR protein directly interacts with the UmuDAb transcription repressor, which possesses some similarities to LexA proteins from other bacteria, to increase the repressors affinity for target sequences in the umuDC operon. These data reveal that DdrR forms a stable complex with free UmuDAb but is released upon association of this repressor complex with target DNA. We show that DdrR also interacts with UmuD, a component of DNA polymerase V and that DdrR enhances the operator binding of LexA repressors from Clostridium difficile, Bacillus thuringiensis and Staphylococcus aureus. Our results suggest that proteins that assist the action of LexA-like transcription factors may be common to many, if not all, bacteria that mount the SOS response.