RNA-Mediated Regulation in Acinetobacter Baumannii Modulates Stress-Induced Phenotypic Variation

In the nosocomial opportunistic pathogen , RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the paradigm, and DDR gene expression in is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding gene regulation is key to elucidate the yet unknown DDR regulation in Here, we identify a structured 5' untranslated region (UTR) in the transcript which serves as a -regulatory element. We show that a predicted stem-loop structure in this 5' UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the 5' UTR influences intracellular RecA protein levels and, , impairing the formation of the stem-loop structure of the 5' UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5' UTR allows for stable transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in may contribute to its success as a pathogen. is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in remains unknown, since unlike most bacteria, does not follow the regulation of the paradigm. In this study, we have started to uncover the mechanisms regulating the novel DDR. We have found that a -acting 5' UTR regulates transcript stability, RecA protein levels, and DNA damage-induced phenotypic variation. Though 5' UTRs are known to provide stability to transcripts in bacteria, this is the first example in which it regulates a bimodal DDR response through transcript stabilization, potentially enabling cells to have enough RecA for survival and genetic variability.