The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic and Oxidative Stress Responses in Acinetobacter
Anna J. Hooppaw, Jenna C. McGuffey, Gisela Di Venanzio, Juan C. Ortiz‐Marquez, Brent S. Weber, Tasia Joy Lightly, Tim van Opijnen, Nichollas E. Scott, Silvia T. Cardona, Mario F. Feldman
Abstract
Acinetobacter baumannii causes a wide range of infections that are difficult to treat due to increasing rates of multidrug resistance; however, the mechanisms that this pathogen uses to respond to stress are poorly understood. 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 A. baumannii's ability to adapt to stress, 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 nonsteroidal anti-inflammatory drugs that could potentially be repurposed as antivirulence therapies to target multidrug-resistant Acinetobacter infections.