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

Abstract

11Acinetobacter baumannii poses a great threat in healthcare settings worldwide with clinical isolates 12 revealing an ever evolving multidrug-resistance. Here, we report the molecular mechanisms 13governing the tight repression of the error-prone DNA polymerase umuDC genes in this important 14 bacterial human pathogen. We demonstrate that the small DdrR protein directly interacts with the 15UmuDAb transcription repressor, which possesses some similarities to LexA proteins from other 16 bacteria, to increase the repressor's affinity for target sequences in the umuDC operon. These data 17 reveal that DdrR forms a stable complex with free UmuDAb but is released upon association of this 18repressor complex with target DNA. We show that DdrR also interacts with UmuD, a component of 19DNA polymerase V and that DdrR enhances the operator binding of LexA repressors from 20Clostridium difficile, Bacillus thuringiensis and Staphylococcus aureus. Our results suggest that 21 proteins that assist the action of LexA-like transcription factors may be common to many, if not all, 22bacteria that mount the SOS response. 23