The phenylacetic acid catabolic pathway regulates antibiotic tolerance and stress responses in Acinetobacter

Acinetobacter baumannii causes a wide range of infections that are difficult to treat due to increasing rates of multi-drug resistance, however, little is understood about the mechanisms used by this organism to respond to stress. Here, we describe a new mechanism of stress signaling in Acinetobacter that is mediated by the metabolite phenylacetic acid (PAA). We found that disrupting PAA catabolism interfered with the stress response of A. baumannii, leading to decreased antibiotic tolerance and hydrogen peroxide resistance. We propose that investigating this stress response could lead to the development of novel therapeutics. In fact, PAA-derivatives constitute a group of FDA-approved non-steroidal anti-inflammatory drugs that could potentially be repurposed as anti-virulence therapies to target multi-drug resistant Acinetobacter infections.