Intracellular Acinetobacter baumannii Acts as a Reservoir in Lung Infection via a ‘Persist and Resist’ Strategy

Although considered primarily extracellular, Acinetobacter baumannii can survive and replicate within macrophages in vitro . Intracellular bacteria are often protected from the host immune system and antibiotic treatment, potentially leading to chronic or recurrent infections. To investigate the role of intracellular A. baumannii during infection, we transferred infected bronchoalveolar lavage fluid (BALF), containing an intracellular bacterial population, to naïve immunocompromised mice. This BALF transfer resulted in A. baumannii lung infection, suggesting that intracellular bacteria may serve as a reservoir for recurrent lung infections. Using dual-proteomics, we characterized the A. baumannii -macrophages interactions. Infected macrophages exhibit an inflammatory and Type I interferon response, marked by increased ACOD1 (IRG1) protein levels. Intracellular A. baumannii upregulates proteins involved in evading nutritional immunity, stress response, surface modification, and metabolic adaptation. These findings suggest that A. baumannii employs a multifactorial strategy to survive and replicate within macrophages, which may contribute to recurrent and chronic infections, and compromise treatment efficacy.