Acinetobacter baumannii is a bacterium resistant to antibiotics and known for causing severe infections, particularly in hospitals. In this study, we compared proteins in healthy human cells and cells infected by A. baumannii to understand how the bacteria cause disease. Our findings reveal that the transcriptional factor FOS becomes much more abundant in human cells during infection. Interestingly, when we used drugs to block FOS, the cytotoxic effects of the bacteria were significantly reduced.

We also discovered that A. baumannii releases small particles called outer membrane vesicles (OMVs) that interact with human cells by activating the aryl hydrocarbon receptor (AHR) receptor. This process begins when the bacterium triggers the activation of an enzyme in human cells called tryptophan-2,3-dioxygenase (TDO). This enzyme produces a molecule called kynurenine, which binds to AHR and causes an increase in the production of the FOS protein.

Our study shows that inhibiting FOS can reduce the severity of A. baumannii infections in both laboratory cell cultures and mice. This finding is particularly significant in the context of the growing antibiotic resistance crisis. We propose that these findings could pave the way for the development of FOS-targeting therapies, offering a new strategy to combat infections caused by multidrug-resistant strains of A. baumannii.