Insights into the mechanism regulating the DNA Damage Response in Acinetobacter baumannii

Acinetobacter baumannii (Ab) is an emerging multidrug‐resistant, opportunistic pathogen. Ab antibiotic resistance acquisition has been linked to its DNA damage response (DDR). DDR genes, including error‐prone DNA polymerases IV (DinB) and V (UmuDC), are involved in DNA damage and desiccation induced mutagenesis. In Escherichia coli , RecA, the cells main recombinase, binds single stranded DNA, the signal of DNA damage, forming the nucleoprotein filament which serves as a co‐protease. It promotes cleavage and inactivation of LexA, the global DDR repressor, resulting in expression of DDR genes. In Ab , this well‐known circuitry does not exist mainly because Ab lacks LexA. We have shown that classical DDR genes in Ab form two phenotypic subpopulations in response to DNA damage: one with low and another with high expression. Our goal is to determine key aspects of Ab 's DDR circuitry and its consequences on survival and antibiotic resistance acquisition. We have focused our attention on understanding the mechanism of recA regulation. We have found that the recA promoter contains non‐conserved novel regulatory elements. We have evidence that different regulatory motifs are important for expression of recA and moreover that deregulation of recA leads to deregulation of umuDC (which has its own unique promoter sequence) . This data suggest that expression of recA has consequences on the expression of error prone DNA polymerase genes forming a regulatory loop, which is typical of bimodal regulation. This unique bimodal DDR may provide a strategy for survival and plasticity in an ever‐changing environment. Supported by RO1 and supplement from the NIH Institute of General Medicine to V.G. Godoy